They describe a characteristic case of cluster headache. It is more frequent in males, the pain is characteristically unilateral periocular of great intensity, of variable duration, usually minutes, and it associates trigeminoautonomic signs such as rhinorrhea and unilateral conjunctival injection. The preventive treatment par excellence is verapamil associated with a descending corticosteroid regimen, as described in answer 2.

They describe a characteristic case of cluster headache. It is more frequent in males, the pain is characteristically unilateral periocular of great intensity, of variable duration, usually minutes, and it associates trigeminoautonomic signs such as rhinorrhea and unilateral conjunctival injection. The preventive treatment par excellence is verapamil associated with a descending corticosteroid regimen, as described in answer [HIDDEN].

A 30-year-old male who consults for unilateral periocular headaches that rapidly progress to become very intense. The pain attacks last 30-60 minutes, occur 2-3 times a day, and are accompanied by tearing in the painful eye and unilateral rhinorrhea. What is the most appropriate preventive treatment?

Oral prednisone with withdrawal in 2-3 months.

Oral prednisone with withdrawal in one month, associated with oral verapamil at a dose of 80-180 mg every 8 hours.

Carbamazepine at doses of 600-1200 mg per day.

Indomethacin at a dose of 50 mg every 8 hours for one month.

The usual treatment of trigeminal autonomic cephalalgias.

Trigeminal autonomic cephalalgias include cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection, tearing, and rhinorrhea (SUNCT). Conventional pharmacological therapy can be successful in the majority of trigeminal autonomic cephalalgias patients. Most cluster headache attacks respond to 100% oxygen inhalation, or 6 mg subcutaneous sumatriptan. Nasal spray of sumatriptan (20 mg) or zolmitriptan (5 mg) are recommended as second choice. The bouts can be brought under control by a short course of corticosteroids (oral prednisone: 60-100 mg/day, or intravenous methylprednisolone: 250-500 mg/day, for 5 days, followed by tapering off the dosage), or by long-term prophylaxis with verapamil (at least 240 mg/day). Alternative long-term preventive medications include lithium carbonate (800-1600 mg/day), methylergonovine (0.4-1.2 mg/day), and topiramate (100-200 mg/day). As a rule, paroxysmal hemicrania responds to preventive treatment with indomethacin (75-150 mg/day). A short course of intravenous lidocaine (1-4 mg/kg/hour) can reduce the flow of attacks during exacerbations of SUNCT. Lamotrigine (100-300 mg/day) is the preventive drug of choice for SUNCT. Gabapentin (800-2700 mg/day), topiramate (50-300 mg/day), and carbamazepine (200-1600 mg/day) may be of help.

Prednisone as initial treatment of analgesic-induced daily headache.

The majority of the patients who seek medical care in tertiary headache centres present with transformed migraine, and convert to daily headache, as a result of excessive intake of symptomatic medications (SM). This study aimed to analyse the possibility of using a short course of oral prednisone for detoxifying patients with chronic daily headache due to medication overuse in an out-patient setting. Four hundred patients with headache occurring more than 28 days per month for longer than 6 months were studied (mean baseline frequency of 0.96). Symptomatic medications were stopped suddenly and prednisone was initiated in tapering doses during 6 days, followed by the introduction of preventive treatment. Withdrawal symptoms and the frequency, intensity and duration of the headache, as well as the consumption of rescue medications, were analysed during the first 16 and 30 days of withdrawal. Eighty-five percent of the patients experienced a reduction in headache frequency and no patients presented severe attacks during the first 6 days. With regard to the following 10 days, 46% of the patients experienced at least 2 days without headache and 58% less intense attacks. Most of the patients noticed attacks with longer duration. After the 30-day period there was a significant decrease in headache frequency (mean 0.83, P<0.001), and no patients returned to overuse of SM. This study demonstrates that it is possible to detoxify patients suffering from rebound headaches, using oral prednisone during the first days of withdrawal, in an out-patient setting.

Giant Cell Arteritis.

Patients with a suspected diagnosis of giant cell arteritis (GCA) should be started on high-dose corticosteroid therapy without delay. A temporal artery biopsy should be performed after initiation of therapy to confirm the diagnosis. Patients with acute visual or neurologic symptoms present a neuro-ophthalmic emergency. Therapy should be initiated immediately with high-dose intravenous methylprednisolone sodium succinate and followed by high-dose oral prednisone. Treatment may begin with high-dose oral prednisone in patients without visual or neurologic symptoms. Calcium, vitamin D, and peptic ulcer prophylaxis should accompany steroid therapy, as indicated. The following treatments should be considered for patients with suspected GCA and acute visual or neurologic signs or symptoms: intravenous methylprednisolone sodium succinate (250 mg intravenously every 6 hours) should be given for 3 days, followed by oral prednisone (80 mg per day or 1 mg/kg) for 4 to 6 weeks. Prednisone should then be tapered by 10 mg per day every month. Most patients require 1 year of therapy to avoid relapse. Taper and duration should be modified according to erythrocyte sedimentation rate, C-reactive protein, and signs and symptoms of GCA. Rheumatologic consultation and follow-up is often helpful for these patients. For patients with suspected GCA and no acute visual or neurologic signs or symptoms, therapy may begin directly with oral prednisone (80 mg per day or 1 mg/kg) with same taper and duration based on laboratory values and clinical signs and symptoms.

Chronic paroxysmal hemicrania

Treatments A ten-patient study conducted by Pareja et al. found that all patients diagnosed with CPH were responsive to indomethacin and were able to completely control their symptoms. Doses of the drug ranged from 25 mg per day to 150 mg per day with a median dose of 75 mg per 24-hour period. Almost all cases of CPH respond positively and effectively to indometacin, but as much as 25 percent of patients discontinued use of the drug due to adverse side effects, namely complications in the gastrointestinal tract. According to a case study by Milanlioglu et al., 100mg of lamotrigine, an antiepileptic drug, administered twice daily alleviated all painful symptoms. No side effects were noted after two months of treatment. Dosage of lamotrigine was decreased to 50mg a day after the first two months, and no symptoms or side-effects were recorded after a three-month followup.

De Quervain Thyroiditis -- Treatment / Management

Treatment for de Quervain thyroiditis is pretty straightforward, with anti-inflammatory treatment being the key. Patients with mild to moderate pain are generally treated with rest and salicylic acid 600 mg orally every 6 hours, naproxen 500 to 1000 mg twice a day, or ibuprofen 400 to 800 mg orally every 8 hours. For more severe neck pain, oral corticosteroids (Prednisone) can be started with 40 mg daily. Usually, symptoms improve in 2 to 3 days with NSAIDS; prednisone should be initiated if no improvement is noted. Steroids should provide pain relief in 1 to 2 days. The typical steroid course can be two months, occasionally longer. The persistence of pain beyond two days should need a further workup for other causes of neck pain. Once pain is improved, an attempt should be made to use the lowest possible dose, and dosing can be titrated by decreasing 5 to 10 mg every week. Recurrent pain should require up-titration of prednisone dose. Unfortunately, prednisone has no role in preventing thyroid dysfunction. [4]

InternalMed_Harrison

Virtually all patients experience a gradual recovery of vision after a single episode of optic neuritis, even without treatment. This rule is so reliable that failure of vision to improve after a first attack of optic neuritis casts doubt on the original diagnosis. Treatment with high-dose IV methylprednisolone (250 mg every 6 h for 3 days) followed by oral prednisone (1 mg/kg per day for 11 days) makes no difference in ultimate acuity 6 months after the attack, but the recovery of visual function occurs more rapidly. Therefore, when visual loss is severe (worse than 20/100), IV followed by PO glucocorticoids are often recommended.

Management of cluster headache.

The prevalence of cluster headache is 0.1% and cluster headache is often not diagnosed or misdiagnosed as migraine or sinusitis. In cluster headache there is often a considerable diagnostic delay - an average of 7 years in a population-based survey. Cluster headache is characterized by very severe or severe orbital or periorbital pain with a duration of 15-180 minutes. The cluster headache attacks are accompanied by characteristic associated unilateral symptoms such as tearing, nasal congestion and/or rhinorrhoea, eyelid oedema, miosis and/or ptosis. In addition, there is a sense of restlessness and agitation. Patients may have up to eight attacks per day. Episodic cluster headache (ECH) occurs in clusters of weeks to months duration, whereas chronic cluster headache (CCH) attacks occur for more than 1 year without remissions. Management of cluster headache is divided into acute attack treatment and prophylactic treatment. In ECH and CCH the attacks can be treated with oxygen (12 L/min) or subcutaneous sumatriptan 6 mg. For both oxygen and sumatriptan there are two randomized, placebo-controlled trials demonstrating efficacy. In both ECH and CCH, verapamil is the prophylactic drug of choice. Verapamil 360 mg/day was found to be superior to placebo in one clinical trial. In clinical practice, daily doses of 480-720 mg are mostly used. Thus, the dose of verapamil used in cluster headache treatment may be double the dose used in cardiology, and with the higher doses the PR interval should be checked with an ECG. At the start of a cluster, transitional preventive treatment such as corticosteroids or greater occipital nerve blockade can be given. In CCH and in long-standing clusters of ECH, lithium, methysergide, topiramate, valproic acid and ergotamine tartrate can be used as add-on prophylactic treatment. In drug-resistant CCH, neuromodulation with either occipital nerve stimulation or deep brain stimulation of the hypothalamus is an alternative treatment strategy. For most cluster headache patients there are fairly good treatment options both for acute attacks and for prophylaxis. The big problem is the diagnosis of cluster headache as demonstrated by the diagnostic delay of 7 years. However, the relatively short-lasting attack of pain in one eye with typical associated symptoms should lead the family doctor to suspect cluster headache resulting in a referral to a neurologist or a headache centre with experience in the treatment of cluster headache.

IL-1β inhibition in autoimmune inner ear disease: can you hear me now?

Clinical vignette: A 51-year-old man with right-sided sudden hearing loss presents to the otology clinic. He has a 4-year history of episodic vertigo of several hours' duration and fluctuating, progressive sensorineural hearing loss in his left ear. The vertigo attacks have not occurred for the last 18 months, and the left ear hearing is consistently poor. The patient's right ear hearing has dropped in the last 36 hours. MRI imaging of brain and temporal bone are normal. A 2-week "burst and taper" of oral prednisone is administered with no effect. Over the next 3 months, serial audiograms show rapidly progressive loss of threshold and word recognition scores on the right side. A trial of high-dose prednisone (60 mg/d for 30 days) results in full recovery of the right ear hearing and substantial improvement in the left ear. As the prednisone dose is slowly tapered over several months, the hearing drops again.

Scleritis -- Treatment / Management -- First-line treatments

Topical corticosteroid eyedrops Can be used in mild cases; some report very limited success Prednisolone acetate 1.0% or difluprednate 0.05% four times per day are options Oral NSAIDs Can start with one agent and switch to another agent if not effective Indomethacin, commonly used, 50 mg, 3 times per day Ibuprofen 600 mg, 3 times per day Naproxen 500 mg, 2 times per day Second-line treatments Oral corticosteroids Prescribed when oral NSAID treatment fails Oral prednisone 1 mg/kg/day; 60 to 80 mg per day Dose continued until one month after the resolution of scleritis, then tapered accordingly Subconjunctival corticosteroid injection Can be used when steroids are contraindicated Controversial use with previous studies of scleral necrosis/perforation More recent reports have indicated improved safety and efficacy of injections Third line treatments

Side-locked headache as the chief complaint of inflammatory orbital pseudotumor (myositic form): a case report.

The case of a 38-year-old woman with continuous unilateral side-locked headache is reported. She had continuous right-sided periorbital pain of mild to moderate intensity for the past 5 months. She also reported a few episodes of pain exacerbations every day. She had no autonomic features. Based on a normal CT scan ordered by her general physician, we started indomethacin (150 mg/day) as well as celecoxib (400 mg/day) for 2 weeks, without relief. Oral prednisone for 6 days provided important relief, and she stayed on daily use of steroids, refusing other forms of therapy. After 5 months she developed orbital and eyelid edema, with painful restrictions to eye movement. Orbital MRI and pathological exam demonstrated inflammatory orbital pseudotumor (myositic form).

[Treatment of acute optic neuritis with high dose of prednisone].

The benefit of glucocorticoid for the treatment of acute optic neuritis remains controversial. The efficacy of oral prednisone in 12 patients (14 eyes) with acute optic neuritis was reviewed. The time of visual symptoms before treatment was 3-15 days. The visual acuities were worse than 0.1 in all patients, with positive relative afferent pupillary defect. Visual field defect and delay latency of P100 in pattern VEP were also found. The regimen of glucocorticoid therapy was oral prednisone, starting with 160 mg daily followed by reducing the dosage by 20 mg every three days until 40 mg per day was attained and then tapering the dosage at 70 mg every other day until stoppage of the drug. The treatment was 3-11 months and 9 patients were followed up more than one year. The visual acuities improved rapidly and stable. After 4 days, the visual acuity was 0.2 or better in 10 eyes. It was better than 0.6 in 12 eyes at 15 days. At 6 months, all had the visual acuity better than 0.7, with 85.7% equal or better than 1.0. The regimen of oral prednisone beginning with 160 mg followed by tapering for three months would be feasible. Pattern VEP was a sensitive and credible sign for evaluating the extent of demyelination.

Immediate and delayed complications of dexamethasone cyclophosphamide pulse (DCP) therapy.

Dexamethasone-cyclophosphamide pulse (DCP) is the prefered mode of therapy in pemphigus in India because it is relatively free from the side effects seen with heavy doses of daily oral steroids. One hundred forty-six pemphigus patients treated with DCP were observed for side effects of this regimen. One hundred forty mg of dexamethasone was administered IV in 200 ml of 5% dextrose over a period of 60-90 minutes on 3 consecutive days. Five hundred mg of cyclophosphamide was added on first day of the pulse and 50 mg given orally daily in the intervening period. DCP was repeated every 4 weeks and continued for 6 months after subsidence of the disease (no new lesions). Flushing over the face was the most common event recorded during the adiministration in 78 subjects followed by palpitations in 11, hiccups in 9, and numbness of feet in 6. Fourteen patients had polyurea, and 3 developed skin rash. Shivering, shooting pains along thighs, breathlessness, seizure and unilateral limb edema were observed in one patient each. Generalized weakness/malaise was the most troublesome delayed side effect in 81 (55.4%) patients; it lasted for 8-15 days after the pulse. Thirty-six (24.6%) had inadequate sleep syndrome, 23 (15.7%) had headache, 21 (14.3%) complained of arthralgias, 19 (13%) experienced alteration in taste, and 13 (9%) had diffuse hair loss. 28 females developed menstrual disturbances, and 14 (9.5%) had blurring of vision (glaucoma in 3 and posterior subcapsular cataract in 1). Thirteen of eighteen diabetics had an increase in blood sugar requiring higher doses of insulin. Five NIDDM patients needed insulin. Four (2.7%) developed hypertension. Pulse therapy is not absolutely free from side effects. Hypertension and diabetes occur less frequently as compared to conventional steroid therapy. Generalized weakness, flushing, headache and taste alteration occur exclusively with pulse therapy.

Limbal Epithelial Transplant -- Technique or Treatment

Allogenic SLET will require long-term oral or pulse intravenous immunosuppression regimens, or else the grafts will eventually reject. The pulse intravenous regimen starts with 500mg IV methylprednisolone on the day of surgery and repeat administration at one-week post-op. This is followed by injections every six weeks until six months post-op, then every two months until one-year post-op, then every three months until two years post-op, and finally,  every six months after that. Oral prednisone is started at 1mg/kg and tapered weekly to 5 mg/day. Patients will also require oral cyclosporine 5 to 7 mg/kg 48 hours pre-op and 1g IV for post-op days 0 to 3. Cyclosporine is then tapered to 1.5 to 2 mg/kg maintenance dose over 4 to 8 weeks, with 90mg of diltiazem hydrochloride to reduce the cost and increase serum cyclosporine levels. Regimens with mofetil and tacrolimus have also been successful. [6] Hepatic, renal, hematologic testing will need to be performed every 4 to 6 weeks. Topical steroid eye drops can be tapered to a maintenance dose of 1 to 2 times/day but can never be tapered off completely. [7]

Gabapentin

The oral bioavailability of gabapentin is approximately 80% at 100 mg administered three times daily once every 8 hours, but decreases to 60% at 300 mg, 47% at 400 mg, 34% at 800 mg, 33% at 1,200 mg, and 27% at 1,600 mg, all with the same dosing schedule. Drugs that increase the transit time of gabapentin in the small intestine can increase its oral bioavailability; when gabapentin was co-administered with oral morphine, the oral bioavailability of a 600 mg dose of gabapentin increased by 50%. Gabapentin at a low dose of 100 mg has a Tmax (time to peak levels) of approximately 1.7 hours, while the Tmax increases to 3 to 4 hours at higher doses. Food does not significantly affect the Tmax of gabapentin and increases the Cmax and area-under-curve levels of gabapentin by approximately 10%.

Headache in a 27-year-old man: Bilateral serous retinal detachment.

A 27-year-old man with a complaint of headache, tinnitus, and visual obscuration presented to a neurologist. Neurologic evaluations, including MRI and CT scan, were within normal limit. The prescribed medicines were propranolol, sumatriptin, valproate sodium, and dexamethasone. Ophthalmic examination was associated with reduction of visual acuity of eyes, bilateral uveitis, and serous retinal detachment. The most probable diagnosis was Vogt-Koyanagi-Harada (VKH) disease. Prescribing high-dose oral steroid and acetazolamide-improved systemic and ocular symptoms. Although HLAB(5) is positive in Behηet disease, it also may be seen in VKH.

Pain management in children

Non-steroidal anti-inflammatory drugs (NSAIDs) Non-steroidal anti-inflammatory drugs (NSAIDs): Used as treatment for pain and as an anti-inflammatory. Can be administered as oral tablet or liquid. It is recommended to use the lowest dose and shortest duration possible to control pain. NSAIDs are not approved for infants under 3 months old. General adverse effects for NSAIDs: Renal impairment Hepatic impairment Gastrointestinal issues (nausea, diarrhea, constipation, flatulence) Dyspepsia Rash Dizziness Abdominal pain Contraindicated for: Hypersensitivity reactions Cardiac impairment Reye's syndrome Coagulation defects Ibuprofen 5–10 mg/kg every 6–8 hours (Max dose 1200 mg/day)

Celecoxib vs prednisone for the treatment of withdrawal headache in patients with medication overuse headache: a randomized, double-blind clinical trial.

To compare the efficacy of celecoxib for treatment of withdrawal headache vs prednisone in patients with medication overuse headache (MOH). In this prospective, double-blind, parallel-group clinical trial, 97 consecutive subjects with MOH were randomized (simple randomization using computer-generated numbers) for treatment with either 400 mg/day celecoxib (for the first 5 days then decreased at a rate of 100 mg every 5 days) or prednisone 75 mg/day orally (for the first 5 days then tapered off every 5 days). Subjects who met the International Headache Society criteria for MOH were included in the trial. The change in headache days and intake of rescue medication were considered as primary outcomes while the change in headache severity defined as a secondary outcome. Patients treated with celecoxib experienced lower headache intensity during the first 3 weeks after withdrawal (after 3 weeks, the median of visual analog scale was 3 for patients in celecoxib group vs 4.5 for prednisone group [P<.001]). However, headache frequency and the need for rescue medication intake were not different between 2 groups. During withdrawal in MOH, in order to reduce headache days or rescue medication intake, using either of celecoxib or prednisone as a bridge is not different.

Management of giant cell arteritis. Our 27-year clinical study: new light on old controversies.

Giant cell arteritis (GCA) is the prime medical emergency in ophthalmology because of its dreaded complication of visual loss in one or both eyes, which is preventable if these patients are diagnosed early and treated immediately and aggressively with systemic corticosteroids. However, there is much controversy on diagnostic criteria and various aspects of steroid therapy to prevent visual loss. We discuss in detail the reasons for the controversy, clinical criteria to establish a definite early diagnosis of GCA, and its management. To provide new information on corticosteroid therapy in GCA, we also present our 27-year planned study on steroid therapy in GCA in 145 temporal artery biopsy-confirmed GCA patients (96 with and 49 without visual loss) seen and followed for 6 weeks or more in our clinic. The median follow-up time was 2.43 years, with interquartile range of 1-6 years (range 6 weeks to 20.2 years). Intravenous megadose steroid therapy was initially given to 33% followed by oral steroids, while the rest had only the oral therapy. The median starting oral prednisone dose was 80 mg/day, with 40% on >/=100 mg/day. We found that the most reliable and sensitive parameters to regulate and taper down steroid therapy were the levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and NOT systemic symptoms. All patients were maintained at the high-dose prednisone till both the ESR and CRP had stabilized at low levels (that usually took 2-3 weeks), after which very gradual tapering of prednisone was started, guided by the ESR and CRP levels only. The median time to reach the lowest maintenance dose of prednisone at which the ESR and CRP stayed low and stable was 48.7 months (95% CI: 34.6, 71.4 months), and the median lowest prednisone dose achieved was 7 mg/day (interquartile range of 1-16 mg/day). A comparison of patients with and without visual loss showed no significant difference in the time to attain the lowest dose (p = 0.359). Our study showed that no generalization is possible for tapering down of prednisone and there is no set formula because of the infinite variation between individuals. Only 10 (7 without visual loss, 3 with visual loss) of 145 patients were able to stop the therapy and maintain stable ESR and CRP levels. We found that only 4% of GCA patients with visual loss showed any visual improvement with high-dose steroid therapy, and 4% developed further visual loss during the first 5 days of high-dose steroid therapy but none after that. Our studies found no evidence that intravenous megadose steroid therapy was more effective than oral therapy in improving vision or preventing visual deterioration due to GCA.

Fosfestrol

Fosfestrol sodium is given at a dosage of 600 to 1200 mg/day by slow intravenous infusion over a period of 1 hour for a treatment duration of 5 to 10 days in men with prostate cancer. Following this, it is given at a dose of 300 mg/day for 10 to 20 days. Maintenance doses of fosfestrol sodium of 300 to 600 mg may be given four times per week. This may be gradually reduced to one 300 to 600-mg dose per week over a period of several months. Fosfestrol sodium is also used to a lesser extent by oral administration initially at a dosage of 360 to 480 mg three times per day in the treatment of prostate cancer. Maintenance doses of 120 to 240 mg three times per day may be used and can be gradually reduced to 240 mg/day. Available forms Fosfestrol is available in the form of solutions for intravenous administration and tablets for oral administration.

Safety and efficacy of prednisone versus placebo in short-term prevention of episodic cluster headache: a multicentre, double-blind, randomised controlled trial.

Prednisone is commonly used for initial short-term therapy of episodic cluster headaches before preventive medication such as verapamil becomes effective, but this strategy has not been tested in large randomised trials. We aimed to access the safety and efficacy of this treatment approach. This study was a multicentre, randomised, double-blind, placebo-controlled trial done in ten specialised headache centres in Germany. Patients with episodic cluster headaches who were aged between 18 and 65 years and within a current pain episode for not more than 30 days, received 100 mg oral prednisone for 5 days followed by tapering of 20 mg every 3 days, or matching placebo (17 days total exposure). All patients received oral verapamil for long-term prevention, starting with 40 mg three times daily and increasing to 120 mg three times daily by day 19; patients then continued with verapamil 120 mg throughout the study. Randomisation was computer-generated at a 1:1 ratio by use of an interactive web-response system, with stratification according to age, sex, and participating site. Participants, investigators, and those assessing outcomes were unaware of treatment allocation. The primary endpoint was the mean number of attacks within the first week of treatment with prednisone compared with placebo. An attack was defined as a unilateral headache with moderate-to-severe intensity of at least five on a numerical rating scale. All efficacy and safety analyses were done in the modified intention-to-treat (mITT) population, which consisted of all patients who had been randomly assigned to a trial group and received at least one dose of prednisone or placebo. The study was stopped early due to slow recruitment and expired funding. The study was registered with EudraCT (2011-006204-13) and with the German Clinical Trials Register (DRKS00004716). Between April 5, 2013, and Jan 11, 2018, 118 patients were enrolled in the study. Two patients dropped out immediately and 116 patients were randomly assigned (57 patients to prednisone and 59 patients to placebo); 109 patients were included in the mITT analysis (53 patients assigned to prednisone and 56 patients assigned to placebo). Participants in the prednisone group had a mean of 7·1 (SD 6·5) attacks within the first week compared with 9·5 (6·0) attacks in the placebo group (difference -2·4 attacks, 95% CI -4·8 to -0·03; p=0·002). Two serious adverse events occurred, both in the placebo group (inguinal hernia and severe deterioration of cluster headache). A total of 270 adverse events were observed: in the prednisone group, 37 (71%) of 52 patients reported 135 adverse events (most common were headache, palpitations, dizziness, and nausea) and in the placebo group, 39 (71%) of 55 patients had 135 adverse events (most common were nausea, dizziness, and headache). Oral prednisone was an effective short-term preventive therapy in our population of patients with episodic cluster headache. Our findings support the use of prednisone as a first-line treatment in parallel to the up-titration of verapamil, although the efficacy of prednisone alongside other long-term prevention requires additional investigation. German Federal Ministry for Education and Research.

Aspirin abolishes spontaneous oto-acoustic emissions.

Spontaneous oto-acoustic emissions (OAEs) were measured prior to, during, and following administration of aspirin. The dose schedule was three 325-mg tablets every 6 h for a total of 16 doses (3.75 days). In every subject studied, all spontaneous OAEs gradually diminished and then disappeared during the drug regimen. Emissions that were initially small disappeared within 14-20 h of beginning the drug regimen (3-4 doses), while initially large emissions took 40-70 h (7-12 doses) to disappear completely. In contrast, the initial size of an emission appeared unrelated to the time required for it to recover to full strength once drug administration ceased. The recovery process was highly idiosyncratic, with the emissions of some subjects returning to full strength within 24 h, while for other subjects, full recovery required several days. In two subjects having multiple emissions in the same ear, the relative sizes of the different emissions often changed greatly during the disappearance and recovery phases. When small frequency shifts appeared for these subjects, they appeared--and were in the same direction--for each of the multiple emissions. In a related experiment, the spontaneous emission was unchanged in one subject who took a drug that inhibits the intracellular entry of calcium ions (verapamil).

Benzodiazepine withdrawal syndrome

The consensus is to reduce dosage gradually over several weeks, e.g. 4 or more weeks for diazepam doses over 30 mg/day, with the rate determined by the person's ability to tolerate symptoms. The recommended reduction rates range from 50% of the initial dose every week or so, to 10-25% of the daily dose every 2 weeks. For example, the reduction rate used in the Heather Ashton protocol calls for eliminating 10% of the remaining dose every two to four weeks, depending on the severity and response to reductions with the final dose at 0.5 mg dose of diazepam or 2.5 mg dose of chlordiazepoxide. For most people, discontinuation over 4–6 weeks or 4–8 weeks is suitable. A prolonged period of reduction for longer than six months should be avoided to prevent the withdrawal process from becoming a "morbid focus" for the person.

Gabapentinoid

The oral bioavailability of gabapentin is approximately 80% at 100 mg administered three times daily once every 8 hours, but decreases to 60% at 300 mg, 47% at 400 mg, 34% at 800 mg, 33% at 1,200 mg, and 27% at 1,600 mg, all with the same dosing schedule. Conversely, the oral bioavailability of pregabalin is greater than or equal to 90% across and beyond its entire clinical dose range (75 to 900 mg/day). Food does not significantly influence the oral bioavailability of pregabalin. Conversely, food increases the area-under-curve levels of gabapentin by about 10%. Drugs that increase the transit time of gabapentin in the small intestine can increase its oral bioavailability; when gabapentin was co-administered with oral morphine (which slows intestinal peristalsis), the oral bioavailability of a 600 mg dose of gabapentin increased by 50%. The oral bioavailability of gabapentin enacarbil (as gabapentin) is greater than or equal to 68%, across all doses assessed (up to 2,800 mg), with a

Prednisolone does not reduce withdrawal headache: a randomized, double-blind study.

Medication overuse headache is a condition where abrupt drug withdrawal is considered the treatment of choice. To study whether prednisolone given orally the first 6 days after medication withdrawal reduces headache intensity during the same period. From August 2003 through November 2005, we included patients aged 18 to 70 years with probable medication overuse headache. The study was randomized, double-blind, and placebo controlled. The patients were hospitalized for 3 days to start medication withdrawal. They were randomly assigned to receive prednisolone 60 mg on days 1 and 2, 40 mg on days 3 and 4, and 20 mg on days 5 and 6 (Group A) or placebo tablets for 6 days (Group B). Headache intensity was recorded in a diary for a month before withdrawal (baseline) and throughout the study period of 28 days. The primary endpoint was a calculated mean headache (MH), based on number of days with headache and mean intensity the first 6 days after withdrawal. We included 26 men and 74 women. Sixty-five had migraine, 13 had tension-type headache, and 22 had both migraine and tension-type headache. Baseline headache days were 25.4 (CI 24.3 to 26.4). Baseline MH was 1.6 (CI 1.41 to 1.69). Fifty-one received Regimen A, and 49 received Regimen B. Baseline features were similar. During the first 6 days after withdrawal, headache was similar in Groups A and B (MH 1.48 [CI 1.28 to 1.68] vs 1.61 [CI 1.41 to 1.82], p = 0.34). Prednisolone has no effect on withdrawal headache in unselected patients with chronic daily headache and medication overuse.

Chronic relapsing inflammatory optic neuropathy

Five diagnostic criteria have been proposed: History of optic neuritis with one relapse Objectively measured visual loss NMO-IgG seronegative Contrast enhancement on imaging of acutely inflamed optic nerves Response to immunosuppressive treatment and relapse on withdrawal or dose reduction Treatment Treatment consists of three phases: 1. Acute phase: IV steroids (methylprednisolone 1 mg/kg) for 3–5 days or plasmapheresis are given to restore visual function. 2. Intermediate phase: Oral steroids (typically prednisone 1 mg/kg) with taper are given to stabilize vision. 3. Long-term phase: To avoid adverse effects of long-term steroids and to avoid relapse of disease, physicians can transition to a steroid-sparing agent. Azathioprine, methotrexate, cyclophosphamide, mycophenolate, IVIG, plasma exchange, cyclosporine, and infliximab have been used.

An Open-Label Study Evaluating the Pharmacokinetics and Safety of Diclofenac Potassium for Oral Solution for the Acute Treatment of MWA or MWoA in Pediatric Participants.

To evaluate the pharmacokinetics, safety, and tolerability of a single 50-mg oral dose of diclofenac potassium for oral solution (OS) in a pediatric cohort with a diagnosis of episodic migraine; the 3-month safety trial following an outpatient dosing period was also evaluated. Children and adolescents often experience migraine pain that is poorly controlled, which may affect their emotional and psychological well-being. Diclofenac potassium for OS is approved for the treatment of migraine with aura (MWA) or migraine without aura (MWoA) in adults 18 years of age or older. It is formulated in a soluble buffered powder that provides more rapid absorption than the tablet formulations of diclofenac potassium. In a randomized, double-blind, crossover trial, more adult patients were pain-free at 2 hours post-dose following treatment with diclofenac potassium for OS than those who received the diclofenac tablet formulation or placebo. This was a Phase 4 open-label study that took place at 2 US sites. Participants 12-17 years of age with a diagnosis of episodic MWA or MWoA for ≥3 months and ≤14 headaches per month were enrolled in the study. Participants received one 50-mg dose of diclofenac potassium for OS under fasted conditions on day 1. Blood samples were collected for PK analysis within 15 minutes pre-dose and at 5, 10, 15, 20, 30, 40, and 60 minutes post-dose, and at 2, 4, and 6 hours post-dose. Safety evaluations were performed after the initial dose and at the end of study on day 90; adverse events were monitored throughout the study. After completing the PK assessments, participants were given a 3-month supply (27 packets) of diclofenac potassium for OS (50-mg doses) for their migraine attacks. Participants were advised to take diclofenac potassium for OS at the onset of a migraine. They were told to take no more than 2 doses daily and not to use it more than 3 days/week. Twenty-five participants completed the study; 84% were females and 96% were white or Caucasian, with a mean age of 15.5 years and a mean weight of 63.1 kg. Diclofenac was rapidly absorbed with a median time to maximum concentration of 15 minutes and a mean peak plasma concentration of 1412 (±846.2) ng/mL. Diclofenac had a half-life of 66.8 (±9.2) minutes. The mean area under the concentration-time curve from zero to the last measurable time point was 82,920.0 (±25,327.6) minutes × ng/mL, and the mean area under the concentration-time curve from time zero to infinity was 84,388.8 (±25,993.6) minutes × ng/mL. Participants took the study drug an average of 10 times over 79 days, with an overall total drug exposure of 506 mg. No deaths or discontinuations due to an AE were reported during the study. The most frequently reported treatment emergent adverse events were arthralgia and motion sickness, each of which occurred in 2 (8%) of the participants. Diclofenac potassium for OS exhibited a favorable pharmacokinetic and safety profile in 12- to 17-year-old patients with a diagnosis of episodic MWA or MWoA.

Individualizing treatment with verapamil for cluster headache patients.

Verapamil is currently the best available prophylactic drug for patients experiencing cluster headaches (CHs). Published papers usually state 240 to 480 mg taken in three divided doses give good results, ranging from 50% to 80%; others mention higher doses--720, even 1200 mg per day. In clinical practice we found we needed to adapt dosage to individual's time of attacks, in particular giving higher doses before going to bed to suppress severe nocturnal episodes. A few only required 120 mg daily. We therefore evolved a scheme for steady and progressive drug increase until satisfactory control had been achieved. To find the minimum dose of verapamil required to prevent episodic and chronic cluster headaches by supervising each individual and adjusting the dosage accordingly. Consecutive patients with episodic or chronic CH (satisfying International Headache Society (IHS) criteria) were started on verapamil 40 mg in the morning, 80 mg early afternoon, and 80 mg before going to bed. Patients kept a diary of all attacks, recording times of onset, duration, and severity. They were advised, verbally and in writing, to add 40 mg verapamil on alternate days, depending on their attack timing: with nocturnal episodes the first increase was the evening dose and next the afternoon one; when attacks occurred on or soon after waking, we advised setting an alarm clock 2 hours before the usual waking time and then taking the medication. Patients were followed-up at weekly intervals until attacks were controlled. They were also reviewed when a cluster period had ended, and advised to continue on the same dose for a further 2 weeks before starting systematic reduction. Chronic cluster patients were reviewed as often as necessary. Seventy consecutive patients, 52 with episodic CH during cluster periods and 18 with chronic CH, were all treated with verapamil as above. Complete relief from headaches was obtained in 49 (94%) of 52 with episodic, and 10 (55%) of 18 with chronic CH; the majority needed 200 to 480 mg, but 9 in the episodic, and 3 in the chronic group, needed 520 to 960 mg for control. Ten, 2 in the episodic and 8 in the chronic group, with incomplete relief, required additional therapy-lithium, sumatriptan, or sodium valproate. One patient withdrew because verapamil made her too tired, another developed Stevens-Johnson syndrome, and the drug was withdrawn. Providing the dosage for each individual is adequate, preventing CH with verapamil is highly effective, taken three (occasionally with higher doses, four) times a day. In the majority (94%) with episodic CH steady dose increase under supervision, totally suppressed attacks. However in the chronic variety only 55% were completely relieved, 69% men, but only 20% women. In both groups, for those with partial attack suppression, additional prophylactic drugs or acute treatment was necessary.

Felbamate

United Kingdom The drug is only available on a limited named-patient basis. Indications and usage Adults: Monotherapy or adjunctive therapy in the treatment of partial seizures, with and without generalization. Children: Adjunctive therapy in the treatment of partial and generalized seizures associated with Lennox-Gastaut syndrome. Dosing Felbamate is available in tablets (400 mg and 600 mg) and as a peach-coloured oral suspension (600 mg/5 mL). Adults (≥ 14 years): begin with 1,200 mg daily given every 6 to 8 hours Children (2–14 years): 15 to 45 mg per kg per day given every 6 to 8 hours

Chronic paroxysmal hemicrania in a 3-year, 10-month-old female.

This is the report of a 3-year, 10-month-old female with classical symptoms of chronic paroxysmal hemicrania and favorable response to indomethacin therapy. The patient was admitted because of frequent episodes of severe unilateral headaches during the day and nighttime as well as agitation. During the episodes, she complained of severe pains on the left orbital and supraorbital region. Subsequent lacrimation from the left eye was also documented. Initially, focal epileptic attack was diagnosed and during the following 10 months several antiepileptic drugs were used without effect. After 10 months, chronic paroxysmal hemicrania was diagnosed because of the typical symptoms along with a favorable response to indomethacin therapy.

Ganciclovir

Pharmacokinetics Absorption of the oral form is very limited—about 5% fasting, about 8% with food. It achieves a concentration in the central nervous system of about 50% of the plasma level. About 90% of plasma ganciclovir is eliminated unchanged in the urine, with a half-life of 2–6 hours, depending on renal function (elimination takes over 24 hours in end-stage renal disease). Administration Acute infections are treated in two phases: induction phase, 5 mg per kilogram intravenously every 12 hours for 14–21 days, the intravenous dose given as a 1-hour infusion maintenance phase, 5 mg per kg intravenously every day Stable disease is treated with 1000 mg orally three times daily. Similar dosing is used to prevent disease in high-risk patients, such as those infected with human immunodeficiency virus (HIV) or those with organ transplants.

[Effects of administration of high dose steroids for complete idiopathic facial nerve palsy: propriety of a second course of steroid therapy].

The purpose of this study was to investigate the existence of any relationship between the initial or total prednisolone dose and the degree of facial nerve recovery in patients with complete idiopathic facial nerve palsy (Bell's palsy). This study was carried out on 102 patients with unilateral complete Bell's palsy of no more than 14 days duration. The patients were divided into four study groups: one receiving a single tapering course of steroids after an initial hydrocortisone (HC) dose of 600 mg, one receiving a second tapering course of steroids after an initial HC dose of 600 mg, one receiving a single tapering course of steroids after an initial HC dose of 1200 mg, and one receiving a second tapering course of steroids after an initial HC dose of 1200 mg. The following variables were analyzed among the groups: the cure rate, the average time needed to achieve maximum recovery, and the rate of side effects. The total cure rate of the patients was 77%. No significant differences were detected among the groups in terms of the cure rate, average time to achieve maximum recovery, or the side effects rate (P > 0.05). High-dose steroid therapy was considered to be somewhat effective in curing complete Bell's palsy. However, there were no correlations between the initial or total steroid dose and the prognosis if a prednisolone equivalent dose of more than 150 mg initially, or a total dose of more than 880 mg was used. These findings show no significant benefits of treating complete Bell's palsy with a second course of steroids.

Darolutamide

The absolute bioavailability of darolutamide with oral administration of a single 300-mg dose without food is approximately 30%. The bioavailability of darolutamide is increased by about 2- to 2.5-fold when administered with food, with a similar increase in exposure occurring for ketodarolutamide. Exposure to darolutamide and ketodarolutamide increases in a nearly linear or dose-proportional manner across a dose range of 100 to 700 mg (or about 0.17- to 1.17-fold the recommended 600-mg dosage). No further increase in exposure to darolutamide was observed at a dosage of darolutamide of 900 mg twice per day (or 1.5 times the recommended 600-mg dosage), indicating a saturation of absorption at doses above 700 mg. Following a single 600-mg dose of darolutamide, peak levels of darolutamide occur after approximately 4 hours. Steady-state levels of darolutamide occur after 2 to 5 days of continuous administration with food, during which time an approximate 2-fold accumulation in darolutamide


We are presented with a case of PANDAS syndrome, a rare complication of an infection caused by group A beta-hemolytic streptococcus.

Given sudden-onset obsessive-compulsive disorder (OCD) in a 9-year-old boy who also has tics and chorea as neurologic manifestations, an infection by should be ruled out:

Streptococcal infection and exacerbations of childhood tics and obsessive-compulsive symptoms: a prospective blinded cohort study.

If pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections is a unique clinical entity, we hypothesized that children meeting diagnostic criteria would have more clinical exacerbations temporally linked to bona fide group A beta-hemolytic streptococcus infection than matched control subjects (chronic tic and/or obsessive-compulsive disorder with no known temporal relationship to group A beta-hemolytic streptococcus infection). Subjects included 40 matched pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections case-control pairs who were prospectively evaluated with intensive laboratory testing for group A beta-hemolytic streptococcus and clinical measures for an average of 2 years. Additional testing occurred at the time of any clinical exacerbations or illness. Laboratory personnel were blinded to case or control status and clinical (exacerbation or not) condition. Clinical raters were blinded to the results of laboratory tests. The cases had a higher clinical exacerbation rate and a higher bona fide group A beta-hemolytic streptococcus infection rate than the control group. Only 5 of 64 exacerbations were temporally associated (within 4 weeks) with a group A beta-hemolytic streptococcus infection, and all occurred in cases. The number (5.0) was significantly higher than the number that would be expected by chance alone (1.6). Yet, >/=75% of the clinical exacerbations in cases had no observable temporal relationship to group A beta-hemolytic streptococcus infection. Patients who fit published criteria for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections seem to represent a subgroup of those with chronic tic disorders and obsessive-compulsive disorder who may be vulnerable to group A beta-hemolytic streptococcus infection as a precipitant of neuropsychiatric symptom exacerbations. Group A beta-hemolytic streptococcus infection is not the only or even the most common antecedent event associated with exacerbations for these patients. Additional intensive studies are needed to determine whether there is clinical or scientific evidence to support separating out subgroups of tic disorder and/or obsessive-compulsive disorder patients based on specific symptom precipitants.

Association between streptococcal infection and obsessive-compulsive disorder, Tourette's syndrome, and tic disorder.

Reports have suggested that streptococcal infection may be etiologically related to pediatric autoimmune neuropsychiatric disorders (PANDAS), but there are few good epidemiologic studies to support this theory. Using population-based data from a large West-Coast health maintenance organization, we assessed whether streptococcal infection was associated with increased risk for obsessive-compulsive disorder (OCD), Tourette's syndrome (TS), or tic disorder. This is a case-control study of children 4 to 13 years old receiving their first diagnosis of OCD, TS, or tic disorder between January 1992 and December 1999 at Group Health Cooperative outpatient facilities. Cases were matched to controls by birth date, gender, primary physician, and propensity to seek health care. Patients with OCD, TS, or tic disorder were more likely than controls to have had prior streptococcal infection (OR: 2.22; 95% CI: 1.05, 4.69) in the 3 months before onset date. The risk was higher among children with multiple streptococcal infections within 12 months (OR: 3.10; 95% CI: 1.77, 8.96). Having multiple infections with group A beta-hemolytic streptococcus within a 12-month period was associated with an increased risk for TS (OR: 13.6; 95% CI: 1.93, 51.0). These associations did not change appreciably when limited to cases with a clear date of onset of symptoms or with tighter matching on health care behavior. These findings lend epidemiologic evidence that PANDAS may arise as a result of a postinfectious autoimmune phenomenon induced by childhood streptococcal infection.

Case study: a new infection-triggered, autoimmune subtype of pediatric OCD and Tourette's syndrome.

A review of clinical observations and literature reports leads to the hypothesis that, via a process analogous to Sydenham's chorea, infections with group A beta-hemolytic streptococci, among others, may trigger autoimmune responses that cause or exacerbate some cases of childhood-onset obsessive-compulsive disorder (OCD) or tic disorders (including Tourette's syndrome). If this hypothesis is correct, then immunological treatments should lead to decreased symptoms in some cases. Four cases with abrupt, severe onset or worsening of OCD or tics are presented from an open treatment study. All were boys aged 10 to 14 years. One had OCD, one had Tourette's syndrome, and two had both OCD and Tourette's syndrome. Clinically and on standardized rating scales, their symptoms were in the moderate to very severe range. Two had evidence of recent group A beta-hemolytic streptococci infections, and the others had histories of recent viral illnesses. Two were treated with plasmapheresis, one with intravenous immunoglobulin, and one with immunosuppressive doses of prednisone. All had a clinically significant response immediately after treatment. Diagnostic criteria are provided that describe these cases of pediatric, infection-triggered, autoimmune neuropsychiatric disorders (PITANDs). Suggestions are made regarding the evaluation and management of patients who may have this condition.

Pediatric autoimmune neuropsychiatric disorders after streptococcus infection.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS) is a group of disorders recently recognized as a clinical entity. A case of PANDAS is described here, which remitted after 1 month of treatment. Recent Group A beta-hemolytic streptococcus infection should be considered in a child who presents with a sudden explosive onset of tics or obsessive compulsive symptoms.

[PANDAS: a possible model for adult OCD pathogenesis].

Obsessive-compulsive disorder is a disabling disorder. Genetic predisposing factors may have an important role in the onset of the symptoms, but is not been individualized any specific gene yet. In the last years it has been demonstrated that obsessive-compulsive disease and/or tic syndromes may be triggered by an antecedent infection especially with group A beta-hemolytic streptococci. On the basis of recent studies has been postulated that in genetically predisposed individuals, certain streptococcal antigens trigger antibodies which, through a process of molecular mimicry, cross-react with epitopes on the basal ganglia. According to such hypothesis, the acronym PANDAS has been used to describe a subset of children with abrupt onset or exacerbations of OCD or tics, or both, following streptococcal infections. Neuroimaging studies reveal increased basal ganglia volumes, and the proposed cause involves the cross-reaction of streptococcal antibodies with basal ganglia tissue. The hypothesis of a possible involvement of the immunitary system seems justified from quantitative alterations of TNF-alpha, IL-6 and IL-1 in the patients' serum with such syndrome. Echotomographic studies on cardiac valves have not yet demonstrated the parallels between PANDAS and Sydenham's chorea. The use of treatment strategies, such as therapeutic plasmapheresis or intravenous immunoglobulin, has been proposed to explain the autoimmune process responsible for the pathogenesis of PANDAS. Further research is still necessary in order to understand the role of streptococcal infection in the pathogenesis of PANDAS.

Obsessive compulsive disorder: is there an association with childhood streptococcal infections and altered immune function?

During the last few years, an increased interest in the possibility of immune mediated pathophysiology of obsessive compulsive disorder (OCD) and related disorders has been seen. In the late 1980s, the National Institute of Mental Health reported an increase of obsessive compulsive symptoms in patients with Sydenham chorea (SC). Subsequently, a precipitating streptococcal infection in children with sudden onset of OCD symptoms but no chorea led to the coining of PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcus). This association has furthered interest in studying immune parameters in non-PANDAS OCD as well. This article will review the neuropsychiatric findings in OCD and Tourette syndrome (TS) with emphasis placed on PANDAS, and its association with SC, and a review of the existing studies that have assessed immunologic measures in patients with OCD and TS.

The evaluation of relationship between group A streptococcal infection with tic disorders in children.

To evaluate the relationship between group A beta hemolytic streptococcus infection (GABHS) and tic disorders in children. This is a case-control study that was conducted in Child and Adolescent Psychiatric Clinic, Isfahan, Iran, between May 2008 and February 2009. Thirty-six children (aged 5-15) with tic and 36 children without tic and obsessive-compulsive disorder (OCD) were investigated for clinical and laboratory signs of GABHS. The tools utilized in this research were clinical interview according to the DSM IV-TR and laboratory tests (throat culture, rapid antigen detection test [RADT], anti streptolysin O [ASO] and yale global tics severity scale [YGTSS]). The control group was of the same gender and age as the tic group who had come to the clinic for other illnesses and was in need of blood test. None of the subjects in the case and control groups had a clinical history of GABHS infection. The relationship between tic disorder and GABHS infection (if any of these laboratory tests takes place: throat culture, RADT, ASO > or = 250) in the tic group was 16 (44.4%) and in the control group was 9 (25%), there were significant differences (p<0.05). No significant correlation was found between ASO titer and YGTSS scores. The specificity of RADT was 100%. The result showed correlation between GABHS infection and tic disorder, but it does not mean that GABHS infection caused tic disorder.

[Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). A report of two cases].

To critically review the past years of research on paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections in children and adolescents. Literature on PANDAS published from 1995 onward was systematically reviewed. The review focuses on definition and diagnostic consideration aetiological and therapeutical issues. To illustrate the clinical characteristic of PANDAS authors present two cases of children with a severe course of obsessive-compulsive disorder and Tourette's syndrome. Post-streptococcal autoimmunity has been postulated as an aetiologic factor in the development of childhood-onset obsessive-compulsive disorder, tic disorders including Tourette's disorder. This hypothesis arose from a series of clinical observations including the documentation of obsessive-compulsive symptoms of children affected by Sydenham's chorea, a variant of rheumatic fever characterised by neurological dysfunction and also by concomitant investigations of childhood-onset OCD and Tourette's syndrome. Results of these studies led to the identification of children whose clinical course is characterised by abrupt and dramatic symptom exacerbations which are temporally related to group A beta-hemolytic streptococcal infections. The identification of such a subgroup will allow for testing of the model of pathogenesis as well as development of novel treatment and prevention strategies. Future research are needed to explore the nature of PANDAS and their relationship with different psychiatric disorders in children and adolescents.

[Acute rheumatic fever, Sydenham's chorea and psychopathology].

Acute rheumatic fever (ARF) is an autoimmune disorder that is triggered by group A beta-hemolytic streptococcal infections. ARF consists of several combinations of carditis, polyarthritis and Sydenham's chorea, and rarely seen erythema marginatum and subcutaneous nodules. Sydenham's chorea is seen in about 20% of patients with ARF. As a late symptom of ARF, Sydenham's chorea usually occurs 3 months or longer after the streptococcal infection. Sydenham's chorea is a neuropsychiatric disorder that may present with emotional lability, anxiety, obsessive compulsive symptoms, attention deficit and hyperactivity symptoms or tics. Obsessive-compulsive symptoms occur in 70% of patients with Sydenham's chorea. The role of the autoimmune mechanisms and the dysfunction of the basal ganglia have been demonstrated in Sydenham's chorea. Antibodies against group A beta-hemolytic streptococcus cross-react with basal ganglia. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) shares the same mechanism with Sydenham's chorea, but PANDAS has not been shown to require penicillin prophylaxis. Thus it is important to distinguish between them. Sydenham's chorea is associated with adulthood OCD, Tourette syndrome and schizophrenia. These features make Sydenham's chorea an explanatory model for obsessive-compulsive disorder (OCD) and related disorders. This poststreptococcal disorder provides a treatment opportunity with new therapies like antibiotic therapy, plasma exchange and intravenous immunoglobulin therapy for psychiatric disorders. In this paper we summarize the phenomenological and treatment studies of OCD, attention deficit and hyperactivity disorder (ADHD), and tic disorders in subjects with ARF, with or without Sydenham's chorea.

A possible association of recurrent streptococcal infections and acute onset of obsessive-compulsive disorder.

Rheumatic fever is an immunologically mediated disease that follows infection by group A beta-hemolytic Streptococcus (GABHS). In rheumatic fever, antibodies generated against GABHS cross-react with the heart, joints, skin, and other sites, inducing an inflammatory, multisystem disease. Brain tissue-specific antibodies have been demonstrated in a subset of children with Sydenham chorea (a component of the Jones criteria for the diagnosis of rheumatic fever), and most Sydenham chorea patients manifest obsessive-compulsive symptoms very similar to those in traditional obsessive-compulsive disorder. The parallels drawn from the paradigm of Sydenham's chorea to Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is an area of active controversy. Newly emerging information on the role of GABHS superantigens in the pathogenesis of rheumatic fever is of particular interest. In this article, we review the microbial characteristics of GABHS and the subsequent immune responses to GABHS as a possible etiology of PANDAS.

A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infections.

Some children with obsessive-compulsive disorder (OCD) and tic disorders appear to have symptom exacerbations triggered by group A beta-hemolytic streptococcal infections in a manner that is similar to rheumatic fever and its neurologic variant, Sydenham's chorea. Because penicillin prophylaxis has proven to be effective in preventing recurrences of rheumatic fever, it was postulated that it might also prevent streptococcal-triggered neuropsychiatric symptom exacerbations in children with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS). These children are identified by five clinical characteristics: presence of OCD or tic disorder, prepubertal onset, episodic symptom course, neurologic abnormalities (i.e., choreiform movements) and streptococcal-triggered symptom exacerbations. Thirty-seven children with PANDAS were enrolled in an 8 month, double-blind, balanced cross-over study. Patients were randomized to receive either 4 months of the active compound (twice daily oral 250 mg penicillin V) followed by 4 months of placebo, or placebo followed by penicillin V. Tic, OCD, and other psychiatric symptoms were monitored monthly. Throat cultures and streptococcal antibody titers were also obtained. There were an equal number of infections in both the active and placebo phases of the study. There was no significant change seen in either the obsessive-compulsive or tic symptom severity between the two phases. Because of the failure to achieve an acceptable level of streptococcal prophylaxis, no conclusions can be drawn from this study regarding the efficacy of penicillin prophylaxis in preventing tic or OCD symptom exacerbations. Future studies should employ a more effective prophylactic agent, and include a larger sample size.

The immunobiology of Tourette's disorder, pediatric autoimmune neuropsychiatric disorders associated with Streptococcus, and related disorders: a way forward.

Obsessive-compulsive disorder (OCD) and related conditions including Tourette's disorder (TD) are chronic, relapsing disorders of unknown etiology associated with marked impairment and disability. Associated immune dysfunction has been reported and debated in the literature since the late 80s. The immunologic culprit receiving the most interest has been Group A Streptococcus (GAS), which began to receive attention as a potential cause of neuropsychiatric symptoms, following the investigation of the symptoms reported in Sydenham's chorea (SC) and rheumatic fever, such as motor tics, vocal tics, and both obsessive-compulsive and attention deficit/hyperactivity symptoms. Young children have been described as having a sudden onset of these neuropsychiatric symptoms temporally associated with GAS, but without supporting evidence of rheumatic fever. This presentation of OCD and tics has been termed pediatric autoimmune neuropsychiatric disorders associated with Streptococcus (PANDAS). Of note, SC, OCD, and TD often begin in early childhood and share common anatomic areas--the basal ganglia of the brain and the related cortical and thalamic sites--adding support to the possibility that these disorders might share a common immunologic and/or genetic vulnerability. Relevant manuscripts were identified through searches of the PsycINFO and MedLine databases using the following keywords: OCD, immune, PANDAS, Sydenham chorea, Tourette's disorder Group A Streptococcus. Articles were also identified through reference lists from research articles and other materials on childhood OCD, PANDAS, and TD between 1966 and December 2010. Considering the overlap of clinical and neuroanatomic findings among these disorders, this review explores evidence regarding the immunobiology as well as the relevant clinical and therapeutic aspects of TD, OCD, and PANDAS.

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: an overview.

The acronym PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been used to describe a syndrome characterized by various obsessions, compulsions, tics, hyperactivity, motor stereotypies, and paroxysmal movement disorders that are correlated with prior infection by group A beta-hemolytic Streptococcus pyogenes (GABHS) infections. Five clinical criteria can be used to diagnose PANDAS: (1) the presence of obsessive-compulsive disorder (OCD) and/or any other tic disorders; (2) prepuberal onset (between 3 years of age and the start of puberty); (3) abrupt onset and relapsing-remitting symptom course; (4) a distinct association with GABHS infection; and (5) association with neurological abnormalities during exacerbations (adventitious movements or motoric hyperactivity). The exact pathogenesis of PANDAS remains unclear, and several theories that focus on multiple etiologic or contributive factors have emerged. PANDAS appears to be a neurobiological disorder that potentially complicates GABHS infections in genetically susceptible individuals. The current standard of care for PANDAS patients remains symptomatic, and cognitive behavioral therapy, such as exposure and response prevention, combined with family counseling and psychoeducation, should be the first approach for treating PANDAS. This review examines current theories of PANDAS pathogenesis, identifies possible treatments for managing this complex condition, and highlights areas for future research. Moving forward, developing more standardized diagnostic criteria and identifying specific laboratory markers to facilitate PANDAS diagnoses are crucial.

Childhood-onset obsessive-compulsive disorder and tic disorders: case report and literature review.

A subgroup of childhood-onset obsessive-compulsive disorder (OCD) and tic disorders has been found to have a postinfectious autoimmune-mediated etiology. Clinical observations and systematic investigations have shown that a subgroup of children with OCD and/or tic disorders have the onset and subsequent exacerbations of their symptoms following infections with group A beta-hemolytic streptococci (GABHS). This subgroup has been designated by the acronym PANDAS: pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. Five clinical characteristics define the PANDAS subgroup: presence of OCD and/or tic disorder, prepubertal symptom onset, sudden onset or abrupt exacerbations, association with neurological abnormalities during exacerbations (adventitious movements or motoric hyperactivity), and the temporal association between symptom exacerbations and GABHS infections. The proposed poststreptococcal inflammatory etiology provides a unique opportunity for treatment and prevention, including immunomodulatory therapies such as plasma exchange and intravenous immunoglobulin. A placebo-controlled trial revealed that both intravenous immunoglobulin and plasma exchange were effective in reducing neuropsychiatric symptom severity (40 and 55% reductions, respectively) for a group of severely ill children in the PANDAS subgroup. Further research is required to determine why the treatments are helpful and to ascertain whether or not antibiotic prophylaxis can help prevent poststreptococcal symptom exacerbations.

[Obsessive-compulsive disorders in children. Subtypes of OCD and their relation to infection with group A streptococci].

The present review describes the theory of a spectrum of obsessive-compulsive disorders (OCD). This spectrum includes such disorders as trichotillomania, eating disorders, body dysmorphic disorder, and possibly pervasive developmental disorders. OCD with an onset in childhood is presented as a specific subtype, with more boys affected and frequently co-morbid with tics and Tourette's syndrome. Furthermore, it seems to be more genetically determined and have more significant deviations, as measured by neuro-imaging studies, than has OCD with an adult onset. The PANDAS theory (paediatric autoimmune neuropsychiatric disorder associated with streptococcal infections) is described. This subtype of OCD is, still on a speculative basis, connected to infections with beta-haemolytic streptococci. The obsessive-compulsive symptoms are characterised by a sudden onset, "sawtoothed" course with relapses and remissions, and are associated with neurological abnormalities. There are still no clinical consequences in terms of penicillin treatment of this PANDAS subtype of OCD.

Obsessive-Compulsive Disorder -- Etiology

The earlier onset of sudden OCD that is preceded by a Streptococcus infection has been known as PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections). Just as Sydenham chorea can present as a sequela from Streptococcus infections, the theory behind OCD is similar in that the strep infection, through molecular mimicry, causes autoimmune antibodies against the basal ganglia leading to obsessive thoughts and compulsive habits. [3] However, the term PANDAS is falling out of favor in lieu of childhood acute neuropsychiatric symptoms (CANS), which allows the development of OCD in the pediatric population to be attributable to other sources than Strep, such as metabolites and toxins. [1]

Is parental report of upper respiratory infection at the onset of obsessive-compulsive disorder suggestive of pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection?

The diagnosis of pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) requires a prospectively determined association between group A beta-hemolytic streptococcal (GABHS) infection and obsessive-compulsive disorder (OCD) or tic disorder. Screening for GABHS infection imposes a significant burden on both patient and clinician. To heighten the index of suspicion for PANDAS, it would be useful to know if parent-reported upper respiratory infection (URI) is associated with PANDAS symptoms or associated characteristics. Eighty-three consecutive, clinically referred patients aged 6 to 17 years with a primary diagnosis of OCD and their primary caregivers were asked about URI signs and symptoms at the time of OCD onset, PANDAS symptoms, OCD and tic symptoms, comorbidity, and putative PANDAS risk factors. Specific inquiry regarding URI symptoms proved more informative than general inquiry. In the URI present versus URI absent group, more patients experienced a sudden rather than insidious onset of symptoms. Additionally, more patients with a URI plus sudden onset exhibited a comorbid tic disorder. Until validated biomarkers permit retrospective diagnosis, a history that OCD began around the time of a URI should clue the clinician to look prospectively for PANDAS. Additional research is required to define the boundaries of PANDAS and to develop psychometrically reliable and valid diagnostic strategies.

Delayed-maturation theory of obsessive-compulsive disorder

Childhood-Onset Obsessive-Compulsive Disorder and Tic Disorders was another experiment that supported the delayed-maturation theory regarding OCD. It was conducted by Snider and Swedo in 2003. Research included the diagnosis of pediatric autoimmune neuropsychiatric disorder, associated with streptococcal infection, also known as PANDAS. Thus, requiring a prospectively determined association between group A beta-hemolytic streptococcal infection, GABHS, and obsessive-compulsive disorder or tic disorder. Screening for a GABHS infection imposes a significant burden on both patient and clinician. To heighten the index of suspicion for PANDAS, it would be useful to know if parent-reported upper respiratory infection, URI, is associated with PANDAS symptoms or associated characteristics. Eighty-three consecutive, clinically referred patients aged 6 to 17 years with a primary diagnosis of OCD and their primary caregivers were asked about. URI signs and symptoms at the time of OCD onset,

Importance of Streptococci Infections in Childhood Neuropsychiatric Disorders.

Paediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS) are important neuropsychiatric disorders in childhood. Streptococcus pyogenes infection associated with tics, obsessive-compulsive disorders, and chorea co-occurrence is important. Swedo et al. have increased the awareness of this situation since 1998. How streptococcal infections give rise to this condition is not clear yet, but the severity of the symptoms is reduced by the treatment of streptococcal infections is important. Eight-year- nine-month-old girl presented with complaints of a 2-year history of upper respiratory tract infections and increased severity of blinking of eyes, throat cleaning, tic disorder and obsession with hand cleaning. In addition, choreiform movements were present and fluoxetine did not improve the symptoms. The patient was followed-up and treated with PANDAS pre-diagnosis. Streptococcus treatment and prophylaxis decreased the patient's complaints. A six-year-four months old boy, admitted with abnormal hand and body movements, which increased severity after the school period, and causing deteriorated fine motor skills during infectious periods for two years. There were also complaints with vocal tics and obsessive-compulsive disorder in the form of throat cleaning. Treatment of S. pyogenes was administered in throat culture. After the penicillin prophylaxis, the complaints decreased. In this study, two patients were presented with choreiform movements, obsessive-compulsive disorder and tic disorder due to follow-up PANDAS diagnosis. PANDAS should be considered in children with neuropsychiatric disorders, especially symptoms associated with infection periods.

Pediatric autoimmune neuropsychiatric disorders associated with Streptococcus in identical siblings.

Termed pediatric autoimmune neuropsychiatric disorders associated with Streptococcus (PANDAS), these cases of childhood-onset obsessive compulsive disorder and tic disorders resemble the presentation of Sydenham chorea, in that they have an acute onset following a group A beta-hemolytic streptococcal infection (group A Streptococcus), with accompanying neurological signs, and an episodic or sawtooth course. Familial associations of this subgroup of patients remain understudied. This report provides phenotypic descriptions of three youth with PANDAS as well as their genetically identical siblings (in two cases of twins and one case of triplets). These cases highlight the potential for environmental influences for discordant presentations in genetically identical siblings. Despite identical genetics, presentations showed marked variation across siblings (from a full PANDAS presentation to asymptomatic). Further research into environmentally driven influences such as postinfectious molecular mimicry and epigenetic factors that may influence the manifestation of these pediatric neuropsychiatric disorders will promote our understanding of their prevention and treatment.

[Streptococcus pyogenes and the brain: living with the enemy].

Streptococcus pyogenes (or group A beta hemolytic streptococcus) is a pathogenic bacterium that can give rise to a range of invasive and autoimmune diseases, although it is more widely known as the cause of tonsillitis. It is particularly interesting to note that this germ only causes disease in humans. For many years it has been acknowledged that it can cause an autoimmune brain disease (Sydenham s chorea). Yet, the spectrum of post streptococcal brain disorders has recently been extended to include other movement disorders such as tics or dystonia. A number of systematic psychiatric studies have shown that certain emotional disorders generally accompany the movement disorder (particularly, obsessive compulsive disorder). The proposed pathogenetic mechanism is that of a neuronal dysfunction in which antibodies play a mediating role. The antibodies that are produced after the streptococcal infection cross react with neuronal proteins, and more especially so in individuals with a propensity. This represents a possible model of immunological mimicry and its potential importance with respect to certain idiopathic disorders such as Tourette syndrome and obsessive compulsive disorder.

PANDAS: current status and directions for research.

The recognition of the five criteria for PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) by Swedo et al established a homogenous subgroup of children with childhood onset obsessive-compulsive disorder (OCD) and/or tic disorders. The five clinical characteristics that define the PANDAS subgroup are the presence of OCD and/or tic disorder, prepubertal age of onset, abrupt onset and relapsing-remitting symptom course, association with neurological abnormalities during exacerbations (adventitious movements or motoric hyperactivity), and a temporal association between symptom exacerbations and a Group-A beta-hemolytic streptococcal (GAS) infection. These five criteria have been used for the purpose of systematic research on the phenomenology and unique therapies for the PANDAS subgroup as well as studies of the pathophysiology of post-streptococcal OCD and tic disorders. The etiology of OCD and tics in the PANDAS subgroup is unknown, but is theorized to occur as a result of post-streptococcal autoimmunity in a manner similar to that of Sydenham's chorea. The working hypothesis for the pathophysiology begins with a GAS infection in a susceptible host that incites the production of antibodies to GAS that crossreact with the cellular components of the basal ganglia, particularly in the caudate nucleus and putamen. The obsessions, compulsions, tics, and other neuropsychiatric symptoms seen in these children are postulated to arise from an interaction of these antibodies with neurons of the basal ganglia.

The PANDAS subgroup: recognition and treatment.

A subgroup of patients with childhood-onset obsessive-compulsive disorder (OCD) has been identified who share a common clinical course characterized by dramatic symptom exacerbations following Group A beta-hemolytic streptococcal (GABHS) infections. The term PANDAS has been applied to the subgroup, to indicate the postulated etiology of their symptoms: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections. Five clinical characteristics define the PANDAS subgroup: presence of OCD and/or tic disorder, prepubertal symptom onset, sudden onset or abrupt exacerbations (sawtooth course), association with neurological abnormalities (presence of adventitious movements or motoric hyperactivity during exacerbations), and temporal association between symptom exacerbations and GABHS infections. Post-streptococcal symptom exacerbations are typically quite dramatic, with patients reporting that their symptoms "...came on overnight" or "...appeared all of a sudden a few days after I had a sore throat." The post-streptococcal inflammatory nature of the neuropsychiatric symptoms provides novel opportunities for treatment and prevention, including immunomodulatory therapies such as therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIG). A recently completed placebo-controlled trial revealed that both IVIG and TPE were effective in reducing neuropsychiatric symptom severity (40% to 55% reductions, respectively) for a group of severely ill children with OCD and/or tic disorders. Further research is required to determine why the treatments are helpful, as well as to ascertain whether or not antibiotic prophylaxis can help prevent post-streptococcal symptom exacerbations.

The PANDAS subgroup of tic disorders and childhood-onset obsessive-compulsive disorder.

Diagnosis and treatment of the PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) variant of Gilles de la Tourette syndrome (GTS) and childhood-onset obsessive-compulsive disorder (OCD) are still controversial issues. Most cross-sectional studies confirm a significant association between GTS and the development of an immune response against group A beta-hemolytic streptococcus (GABHS). Moreover, longitudinal retrospective studies suggest that a recent exposure to GABHS might be a risk factor for the onset of tics and obsessive-compulsive symptoms. However, further evidence from longitudinal prospective research is needed to verify whether a temporal association between GABHS infections and symptom exacerbations is a useful and reliable criterion for the diagnosis of PANDAS. In addition, preliminary results suggest that the PANDAS spectrum might be enlarged to include attention deficit/hyperactivity disorder. Although a number of immunological biomarkers have been proposed as markers of the PANDAS variant, at present, none of these has been conclusively proved useful to diagnose and monitor disease course in children with a suspicion of PANDAS. Finally, despite their empirical use in community settings, we still lack conclusive, evidence-based data regarding the usefulness of antibiotic and immunomodulatory treatments in children with PANDAS. Given the relevance of this topic for general pediatric health, additional research efforts to solve all the pending issues and the hottest points of debate are warranted.

PANDAS

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) is a controversial hypothetical diagnosis for a subset of children with rapid onset of obsessive-compulsive disorder (OCD) or tic disorders. Symptoms are proposed to be caused by group A streptococcal (GAS), and more specifically, group A beta-hemolytic streptococcal (GABHS) infections. OCD and tic disorders are hypothesized to arise in a subset of children as a result of a post-streptococcal autoimmune process. The proposed link between infection and these disorders is that an autoimmune reaction to infection produces antibodies that interfere with basal ganglia function, causing symptom exacerbations, and this autoimmune response results in a broad range of neuropsychiatric symptoms.

MRI assessment of children with obsessive-compulsive disorder or tics associated with streptococcal infection.

The authors assessed selective basal ganglia involvement in a subgroup of children with obsessive-compulsive disorder (OCD) and/or tics believed to be associated with streptococcal infection. Using computer-assisted morphometric techniques, they analyzed the cerebral magnetic resonance images of 34 children with presumed streptococcus-associated OCD and/or tics and 82 healthy comparison children who were matched for age and sex. The average sizes of the caudate, putamen, and globus pallidus, but not of the thalamus or total cerebrum, were significantly greater in the group of children with streptococcus-associated OCD and/or tics than in the healthy children. The differences were similar to those found previously for subjects with Sydenham's chorea compared with normal subjects. These results support the hypothesis that there is a distinct subgroup of subjects with OCD and/or tics who have enlarged basal ganglia. These findings are consistent with the hypothesis of an autoimmune response to streptococcal infection.

No Cases of PANDAS on Follow-Up of Patients Referred to a Pediatric Movement Disorders Clinic.

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) remains a controversial diagnosis and it is unclear how frequently it is encountered in clinical practice. Our study aimed to determine how many children with acute-onset tics and/or Obsessive-Compulsive Disorder (OCD) met criteria for PANDAS. A retrospective review was performed on 39 children who presented to a movement disorders clinic with acute-onset tics or OCD from 2005 to 2012. Out of 284 patients seen over the course of 7 years, only 39 had acute-onset tics and/or OCD symptoms. None of the 39 children who presented to us acutely met full criteria for PANDAS. Thirty-eight percent had no association between their symptoms and group A beta-hemolytic streptococcal infection, while 54% had prior inconclusive laboratory testing done and no exacerbations during the course of the study. Only 8% of patients had an acute exacerbation after their initial visit; however, testing for GAHBS in these patients was negative Discussion: Our results support the notion that PANDAS, if it exists, is an exceedingly rare diagnosis encountered in a pediatric movement disorder clinic. While none of our patients met criteria for PANDAS, two with acute-onset OCD would have met criteria for pediatric acute-onset neuropsychiatric syndrome (PANS) indicating that PANS may be a more appropriate diagnosis.

Case series: increased vulnerability to obsessive-compulsive symptoms with repeated episodes of Sydenham chorea.

The association between obsessive-compulsive symptoms (OCS) and Sydenham chorea (SC) supports the hypothesis of a common neuroimmunological dysfunction in basal ganglia associated with group A beta-hemolytic streptococcal infection underlying both conditions. Four children with 2 distinct SC episodes were evaluated to assess the course of OCS. All patients developed OCS during their second episodes (3 met criteria for obsessive-compulsive disorder [OCD]), but not in their first episodes (2 developed OCS and met criteria for OCD). These data suggest that the recurrence of SC episodes may result in a cumulative effect, thus increasing the risk of appearance and intensification of OCS.

Obsessive-compulsive symptoms in adults with history of rheumatic fever, Sydenham's chorea and type I diabetes mellitus: preliminary results.

Rheumatic fever (RF) associated with Sydenham's chorea (a neurological variant of RF), but not RF without chorea, has been acutely related to obsessive-compulsive symptomatology/disorder (OCS/OCD). This study investigated the presence of OCS in adults who had RF with or without chorea in childhood. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used to evaluate OCS in 38 adults with history of RF (13 with chorea; 25 without chorea) or diabetes (controls; n = 19). The OCS was similar in both groups, although the intensity of symptoms was not clinically relevant. Moreover, subjects with RF with or without chorea did not score differently in the Y-BOCS. The similar occurrence of OCS in patients with history of RF and diabetes suggests that the development of this symptomatology, triggered by group A beta-haemolytic streptococcus infections, is restricted to the RF acute phase, occurred during infancy, and did not seem to predispose the appearance of OCS in adulthood.

Infection-triggered anorexia nervosa in children: clinical description of four cases.

Anorexia nervosa (AN) is a serious illness with no definitive treatment. Clinical and research evidence led to the hypothesis that some children with AN may have a pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS), similar in pathogenesis to other hypothesized PANDAS disorders. Four youngsters (ages, 11-15 years) with PANDAS AN were treated with an open trial of antibiotics, in addition to conventional treatment. They were evaluated for eating disorder and obsessive-compulsive symptoms, and for weight gain. Evidence of streptococcal infection came from clinical evaluation, throat cultures, and two serological tests: anti-deoxyribonuclease B (anti-DNase B) and anti-streptolysin O (ASO) titers. The "rheumatic" marker D8/17 was also measured. This B-cell alloantigen is associated, in several publications, with poststreptococcal autoimmunity: Rheumatic fever (RF), Sydenham's chorea (SC), and possibly PANDAS obsessive compulsive disorder (OCD) and tic disorders. There was clinical evidence of possible antecedent streptococcal infection in all four patients, two of whom had comorbid OCD, with possible infection-triggered AN. All four had the rheumatic marker: A percentage of D8/17-positive B cells of 28-38%, with a mean of 33% (12% or more is considered positive for the marker). The patients responded to conventional treatment plus antibiotics with weight restoration and decreased eating disorder and obsessive-compulsive symptoms. Three needed to gain weight and did so. There may be a link between infectious disease and some cases of AN, which raises the possibility of new treatment.

[Evaluation of a Neuropsychiatric Disorder: From PANDAS to PANS and CANS].

PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) syndrome is a disorder seen before adolescence that possesses an abrupt onset of obsessive-compulsive disorder symptoms and/or tics. Swedo and colleagues defined this disorder in 1998 as a syndrome related to Group A streptoccoccus (GAS) infection with neurological issues, such as motor hyperactivation and choreiform movements. The progress of the disorder may be described as wax-and-waning, apart from abrupt onset, and this relapse and remission course is associated with exacerbating infections, according to the creators of PANDAS syndrome. Ruling out of Rheumatoid Fever and Sydenham's Chorea was a necessity for making a proper diagnosis. Since the recognition of this syndrome, clinicians encountered many children who could not fulfill all 5 criteria, which must be met for PANDAS diagnosis. In addition, due to literature showing failure and lack of strong evidence of a major role of GAS, the newly-defined categories PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) and CANS (Childhood Acute Neuropsychiatric Syndrome) were created to encompass those of "almost met" non-PANDAS cases. PANS and CANS include concurrent significant psychiatric symptoms with abrupt onset of OCD symptoms and/or tics but do not require identification of any infection agent, immune dysfunction, or enviromental precipitants. In this paper, we aimed to discuss PANS/ CANS, alterations of PANDAS, and diagnoses in which "almost met" PANDAS patients should be classified on the basis of a case who developed an abrupt onset of anxiety, obsessions, and vocal tics.

[Pediatric acute-onset neuropsychiatric syndrome: clinical/laboratory characteristics].

Based on the current conceptions on the genesis of hyperkinetic syndromes in children and adolescents, to single out a group of patients with suggestive PANS, compare clinical and laboratory results and determine clinical/laboratory characteristics of this syndrome. Sixty-nine patients with tics were studied using neurological examination, questionnaires and international scales for assessment of tics, obsessive-compulsive disorders and attention deficit hyperactivity disorder (ADHD). Laboratory tests included general blood tests, antistreptolysin O test, determination of rheumatoid factor, C-reactive protein, circulating immune complexes, nasopharyngeal wash for β-hemolytic streptococcus, antineuronal antibodies and immunoglobulins A, M, G, E, CD4, CD8-lymphocytes. The same tests were performed in the control group. Clinical symptoms were different by the severity and phenomenology of tic hyperkineses in patients with PANS compared to the patients with tics without immune disorders. Most of the patients were diagnosed with Tourette syndrome. ADHD was the most common diagnosis in the PANS group. Its frequency was 2.5 higher in the male patients. A chronic focus of infection did no predict the development of PANS. Based on the laboratory results, one can assume that β-hemolytic streptococcus A infection, lower JgM levels and an elevated CD8+ lymphocytes predict the development of autoimmune mental and neurological disorders in the group of PANS patients.