bluuebunny/crossref_metadata_2025 huggingface dataset:
Methylprednisolone May Improve Lumbosacral Radiculoplexus Neuropathy
Authors: Dyck P. James B. , Norell Jane E. , Dyck Peter James
Published: December 2014

Objective:

To report on an open trial of intravenous methylprednisolone (IV MP) in nondiabetic lumbosacral radiculoplexus neuropathy (LSRPN).

Background:

Lumbosacral radiculoplexus neuropathy is a subacute, unilateral or asymmetric syndrome of pain, weakness, and paresthesia of the lower extremity, which is attributed to ischemic injury from microvasculitis in lumbosacral roots, plexus, and nerves.

Methods:

Eleven nondiabetic patients with worsening LSRPN were treated - ten with infusions of IV MP (1 gm/wk) for 8 to 16 weeks and one with an equivalent dosage of oral prednisone. The main endpoints evaluated were: 1) the Neuropathy Impairment Score (NIS), and 2) the Neuropathy Symptoms and Change (NSC) scores.

Results:

The median age of our patients was 67 years, range 49 to 86 years. Seven patients were women. All 11 patients reported improvement during treatment - nine reported marked improvement. The median NIS improved from 42 points (range 9 to 106 points) before treatment, to 20 points (range 5 to 57 points) (p = 0.005) after treatment. Pain was completely resolved in four patients and much improved in seven. The change subscore and the severity subscore of the NSC were statistically significantly improved after treatment. Prior to treatment, all patients had significant weakness with six confined to wheelchairs and four using mechanical devices to aid in ambulation. After treatment, the weakness was markedly improved in nine patients; only one still required a wheelchair and six walked independently (p = 0.03).

Conclusion:

1) In LSRPN, pain and neurological deficits improved (often dramatically) with IVMPtreatment. 2) Although our results should be interpreted with caution since this trial is uncontrolled, IV MP may favorably affect the natural history of LSRPN. 3) The results are sufficiently promising to provide a rationale for prospective, sham controlled, double blind trials.
Non-Atherosclerotic Fusiform Cerebral Aneurysms
Authors: Findlay J. Max , Hao Chunhai , Emery Derek
Published: December 2014

Background:

Fusiform cerebral aneurysms are dilatations of the entire circumference of a segment of cerebral artery, usually considered due to atherosclerosis in adults. They are relatively thick-walled and elongated, causing neural compression or ischemia when discovered. We have noted a subset of fusiform cerebral aneurysms that vary from this common description.

Patients:

Out of a series of 472 intracranial aneurysms treated over 11 years, 11 patients between the ages 16 and 67 years (mean age 37) were identified who had discrete fusiform aneurysms unassociated with generalized cerebral atherosclerosis, connective tissue disorder or inflammation. Three presented with hemorrhage, six with neural compression by the aneurysm and two were discovered incidentally.

Results:

Nine aneurysms were located in the posterior circulation, the other two in the intracranial carotid artery. Their mean length and width were 16.3 and 11 mm, respectively. Three aneurysms contained thrombus. The eight aneurysms that were exposed surgically were partly or substantially thin-walled with normal appearing parent arteries. Eight were treated with proximal occlusion and three were circumferentially “wrapped”. Parent artery occlusion caused one death and one mild disability and the remaining patients made good recoveries (follow-up 0.5 - 10 years).

Conclusions:

There is a subset of cerebral aneurysms with discrete fusiform morphology, apparently unrelated to cerebral atherosclerosis or systemic connective tissue disease, thin-walled in part or whole, more common in the vertebrobasilar system, and possessing a risk of rupture. Treatments currently available include proximal occlusion or aneurysm “wrapping”, different approaches than neck-clipping or endovascular coiling of side-wall saccular cerebral aneurysms that leave the parent artery intact.
Convulsive Status Epilepticus in Children with Intractable Epilepsy is Frequently Focal in Origin
Authors: Jan Mohammed M.S. , Neville Brian G.R. , Cox Timothy C. , Scott Rod C.
Published: December 2014

Background:

Convulsive status epilepticus (CSE) is a common neurological emergency. Our objectives were to study children with recurrent nonfebrile CSE to assess the evidence for focal origin.

Methods:

Series of 18 children with recurrent CSE and intractable epilepsy were identified by chart review. Clinical, radiological, and EEG data were reviewed. Focal structural abnormalities were identified on MRI and CT images by one neuroradiologist who was unaware of the clinical details.

Results:

The patient's ages ranged between 6-22 years (mean 15.3, SD 4), and 67% were males. Most children (89%) had a severe cognitive and / or behavioural disorder. Most patients (89%) had multiple seizure types and 95% of these were partial seizures. Twelve (67%) children had at least one episode of CSE with focal features identified clinically. Focal brain abnormalities were detected on 18% and 55% of CTand MRI films respectively. Overall, 53% had a focal abnormality on structural neuroimaging. Interictal EEG revealed focal or multifocal abnormalities on at least one occasion in 94% and 22% of patients respectively. Overall, 17 patients had focal features on at least one EEG. Thirteen ictal EEGs were recorded on 11 (61%) patients. Ten (91%) of these recordings revealed a focal onset.

Conclusions:

Many handicapped children with recurrent CSE have focal clinical, radiological, or electrographic features. This supports a focal origin for CSE in most children with intractable epilepsy.
Nipah encephalitis outbreak in Malaysia, clinical features in patients from Seremban
Authors: Chong Heng Thay , Kunjapan Sree Raman , Thayaparan Tarmizi , Geok Tong Jenny May , Petharunam Vijayasingham , Jusoh Mohd Rani , Tan Chong Tin
Published: December 2014

Background:

An outbreak of viral encephalitis occurred among pig industry workers in Malaysia in September 1998 to April 1999. The encephalitis was attributed to a new paramyxovirus, Nipah virus. This is a description of the clinical features of 103 patients treated in the Seremban Hospital with characterization of the prognostic factors.

Methods:

Clinical case records and laboratory investigations were reviewed. The case definition was: patients from the outbreak area, direct contact or in close proximity with pigs, clinical or CSF features of encephalitis.

Results:

The mean age was 38 years, 89% were male, 58% were ethnic Chinese, 78% were pig farm owners or hired workers. The mean incubation period was 10 days. The patients typically presented with nonspecific systemic symptoms of fever, headache, myalgia and sore throat. Seizures and focal neurological signs were seen in 16% and 5% respectively. In the more severe cases, this was followed by drowsiness and deteriorating consciousness requiring ventilation in 61%. Autonomic disturbances and myoclonic jerks were common features. The mortality was high at 41%. Systolic hypertension, tachycardia and high fever were associated with poor outcome. On the other hand, 40% recovered fully. As for the other 19%, the residual neurological signs were mostly mild.

Conclusion:

Nipah virus caused an encephalitis illness with short incubation period and high mortality. The prognosis for the survivors was good.
Global Cerebral Anoxia
Authors: Chan Jean-Wen , Bell Kathleen E.
Published: December 2014

A 57-year-old, previously healthy tourist sustained closedhead trauma during a high-speed motor vehicle collision. She was found unconscious at the scene with a Glasgow coma scale score of 3. She suffered a multitude of injuries including frontal scalp lacerations and cervical cord injury. Upon arrival at the hospital, she suffered cardiopulmonary arrest of up to 12 minutes without a perfusing rhythm and was intubated.
Communication Issues in Migraine Diagnosis
Authors: Edmeads John
Published: December 2014

Objectives:

To examine the importance of good communication when informing the patient of the diagnosis of migraine; to review the essentials of successful communication between physician and patient on the aspect of diagnosis; to survey learning resources for physicians on communicating information to patients.

Methods:

This paper is based on observations made by the author of the successful interactions of numerous international “headache experts” with their patients, on a review of the medical education literature pertaining to the teaching of communication skills, and on 30 years of not always successful communication with patients.

Results:

Communicating the diagnosis of migraine is an opportunity to educate and reassure the patient, to lay the foundation for rational treatment and to help establish the successful doctor-patient relationship which is essential for effective management. No matter how accurate the diagnosis, failure to communicate it effectively to the patient (and often to significant others) may impair interactions with the patient and compromise therapy. Effective communication of a diagnosis requires clarity, relevance to the patient, a positive attitude, and reinforcement through repetition, questioning and dialogue. In terms of using the diagnosis to lay a foundation for therapy, it is useful to explain the symptoms as transient physical dysfunction of normal tissues, to indicate that there are multiple mechanisms underlying the dysfunction of which only some may presently be susceptible to treatment and to stress the relevance of emotions as factors which may powerfully affect, for better or worse, the underlying disturbed physiology of migraine. Into this model can be “plugged” all the relevant therapies for migraine. This is the ideal, but every day experience in the headache consultant's office suggest that in both primary care and specialist practice, it is infrequently attained. There are scant resources other than example for physicians to learn communication of headache diagnosis specifically but there are numerous print and web resources available to physicians who wish to learn and/or teach the generic principles of effective communication, and these principles require little or no modification to be applied to the headache patient and the headache doctor.
Glioblastoma Multiforme and Ascending Weakness
Authors: Cooke L.J. , Morrish William , Becker W.J.
Published: December 2014

An 18-year-old man with a known glioblastoma multiforme, previously treated with de-bulking, chemotherapy, radiation and steroids, underwent a repeat craniotomy after presenting with several days of intractable vomiting and headache. Postoperatively, he developed progressive delirium, bilateral sixth and seventh nerve palsies, dysphagia and ascending weakness of the upper and lower limbs. Within five postoperative days, he was quadraparetic, areflexic and had marked extraocular muscle and facial weakness, dysphagia, dysphonia and respiratory muscle weakness. The patient was started empirically on intravenous immunoglobulin for suspected Guillain-Barré syndrome (GBS). The following day, lumbar puncture demonstrated elevated protein (1.96g/l; normal <0.45), and a reduced glucose (0.5 mmol/l) and elevated red (4125x106 per litre) and white cell (214x106 per litre) counts in the cerebrospinal fluid (the red cells were felt to be related to surgery). The cell differential included 69% neutrophils, 3% lymphocytes, 15% monocytes and 13% blast-like cells. Gram stains and cultures of the cerebrospinal fluid were negative.
Chronic (Rasmussen’s) Encephalitis in an Adult
Authors: Wennberg Richard , Nag Sukriti , McAndrews Mary-Pat , Lozano Andres M. , Farb Richard , Mikulis David
Published: December 2014

A 24-year-old woman was referred because of incompletely-controlled complex partial seizures. Her seizures had started at age 21, after a mild head injury with brief loss of consciousness incurred in a biking accident, and were characterized by a sensation of bright flashing lights in the right visual field, followed by numbness and tingling in the right foot, spreading up the leg and to the arm, ultimately involving the entire right side, including the face. Occasionally they spread further to involve right facial twitching with jerking of the right arm and leg, loss of awareness and, at the onset of her epilepsy, rare secondarily generalized convulsions. Seizure frequency averaged three to four per month. She was initially treated with phenytoin and clobazam and subsequently changed to carbamazepine 800 milligrams per day. She also complained that her right side was no longer as strong as her left and that it was also numb, especially the leg, but felt that this weakness had stabilized or improved slightly over the past two years.
Dural Cavernous Angioma: A Preoperative Diagnostic Challenge
Authors: Rosso Dominic , Lee Donald H. , Ferguson Gary G. , Tailor Chetna , Iskander Sam , Hammond Robert R.
Published: December 2014

Background:

Dural cavernous angiomas are uncommon benign vascular malformations which may present intraoperative difficulties in hemostasis when the diagnosis is not suspected preoperatively. Preoperative diagnosis can be difficult when angiomas show atypical features and share imaging characteristics with other entities.

Methods:

A patient presented with a radiographically aggressive lesion, subsequently identified as a dural cavernous angioma. The lesion is reviewed and its clinical, radiographic, and pathological features are compared with other vascular malformations.

Case report:

A 40-year-old man presented with new onset seizures and an enhancing lesion infiltrating the floor of the right middle cranial fossa. Due to its aggressive radiographic appearance, initial considerations included chondrosarcoma, meningioma or metastasis. Pathological examination, however, revealed the lesion to be a cavernous angioma of dura.

Conclusion:

This uncommon lesion may present a diagnostic challenge with significant intraoperative implications. T2 sequence hyperintensity in a relevant lesion should raise suspicion of an hemangioma. It is important to be aware of this entity and its potential to mimic other entities on radiographic grounds.
Progress in Clinical Neurosciences: Therapeutic Hypothermia in Severe Traumatic Brain Injury
Authors: Zygun David A. , Doig Christopher J. , Auer Roland N. , Laupland Kevin B. , Sutherland Garnette R.
Published: December 2014

Severe traumatic brain injury (sTBI) is a relatively common problem with few therapies proven effective. Despite its use for over 50 years, therapeutic hypothermia has not gained widespread acceptance in the treatment of sTBI due to conflicting results from clinical trials. This review will summarize the current evidence from animal, mechanistic and clinical studies supporting the use of therapeutic hypothermia. In addition, issues of rewarming and optimal temperature will be discussed. Finally, the future of hypothermia in sTBI will be addressed.
Chlamydia pneumoniae and Atherosclerosis following Carotid Endarterectomy
Authors: Jahromi Babak S. , Hill Michael D. , Holmes Kate , Hutchison Stuart , Tucker William S. , Chiu Brian
Published: December 2014

Background:

Seroepidemiological studies have shown an association between raised antibody titres against Chlamydia pneumoniae, and carotid atherosclerosis or stroke. However, direct evidence for a causal link between arterial infection with C. pneumoniae and carotid disease remains weak. We hypothesized that long-term follow-up of patients with pathologically-proven arterial C. pneumoniae infection might provide further insight into the role of C. pneumoniae in carotid atherosclerosis.

Methods:

We followed a cohort of 70 carotid endarterectomy patients for ipsilateral restenosis, contralateral progression, and all-cause mortality (four year median follow-up period). All patients had presence or absence of C. pneumoniae in their carotid plaques documented by immunohistochemistry after endarterectomy. A survival function was generated and the log-rank test was used to assess the difference in survival between subjects with and without documented chlamydial infection in their plaque.

Results:

Baseline demographic and cardiovascular risk factors were similar between the two groups, and survival analysis demonstrated no difference (p>0.05) in all-cause mortality, or all-cause mortality combined with restenosis and progression.

Conclusion:

Our data finds no causal role for C. pneumoniae in restenosis or progression of carotid disease or mortality in this patient population with advanced carotid atherosclerosis.
Clinical and Research Advances in Huntington's Disease
Authors: SuttonBrown M. , Suchowersky O.
Published: December 2014

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by abnormalities of movement and dementia. No curative treatment is available and HD results in gradually increasing disability. Characterization of the genetic abnormality has dramatically increased our understanding of the underlying mechanisms of the disease process, and has resulted in the development of a number of genetic models. These research tools are forming the basis of advanced work into the diagnosis, pathophysiology, and potential treatment of the disease. Clinically, the availability of genetic testing has eased confirmation of diagnosis in symptomatic individuals. Presymptomatic testing allows at-risk individuals to make informed choices but requires supportive care from physicians. Current clinical treatment is focused on symptom control. Advances in research have resulted in the development of potential neuroprotective strategies which are undergoing clinical testing.
TAU Mutations are not a Predominant Cause of Frontotemporal Dementia in Canadian Patients
Authors: Levchenko Anastasia , Robitaille Yves , Strong Michael J. , Rouleau Guy A.
Published: December 2014

Objective:

Frontotemporal dementia is a neurodegenerative disease affecting mostly the frontal and/or temporal lobes, with neuronal loss and intraneuronal and/or intraglial inclusions composed of hyperphosphorylated microtubule-associated protein tau and ubiquitin. Missense and splice site mutations in the TAU gene have been identified in approximately 15% of all frontotemporal dementia cases. In this study, we evaluated the involvement of mutations in the TAU gene in development of frontotemporal dementia phenotype in patients of French or English Canadian origins.

Methods:

Fourteen patients with frontotemporal dementia phenotype and 98 normal controls were recruited for the study. The TAU gene was screened by sequencing and denaturing high performance liquid chromatography.

Results:

No mutations, except some new polymorphisms, were detected in the TAU gene of these patients. One polymorphism, however, may play a role in pathogenesis.

Conclusion:

Our results agree with previous work suggesting that mutations in this gene are not a frequent cause of the frontotemporal dementia phenotype in Canadian patients.
Distortion of Normal Pituitary Structures in Sellar Pathologies on MRI
Authors: Sade Burak , Mohr Gérard , Vézina Jean Lorrain
Published: December 2014

Objective:

This study was undertaken to assess the displacement patterns and shifts of the normal pituitary gland in sellar pathologies on MRI and to determine if the position of the bright spot (BS) represents a predicting factor for the position of the residual adenohypophysis (RAH) in pathological conditions.

Methods:

In a control group of 102 patients without any pituitary pathology, the presence of the BS was evaluated. In 100 patients with intra- or suprasellar pathologies, presence and respective topography of BS and RAH were scrutinized on MRI, according to lesion type, size, endocrine status and intra-operative findings in the surgical group.

Results:

The BS was visible in 91.2% of 102 cases in the control group, as compared to 75 of the 100 patients with sellar lesions. Location of RAH was identified in 58% of the patients, and RAH enhanced more than the lesion in all cases after contrast infusion. The RAH was identified in 65.3% of the 75 “BS positive” patients, as compared to 36% of the 25 “BS negative”. The normal residual gland was visualized intra-operatively in 63.5% of the 52 operated patients: in 37 “BS positive” patients, it was visualized intra-operatively in 81.1% and in 28 “RAH positive” patients, it was identified in 82.1%.

Conclusion:

The BS can be identified in the majority and RAH in more than half of the cases with pituitary lesions on MRI. Positions of both the BS and RAH help predict the location of the normal residual gland during surgery and, therefore, may contribute to preserving the pituitary function.
Controversies in Cervical Discectomy and Fusion: Practice Patterns Among Canadian Surgeons
Authors: Pickett Gwynedd E. , Soelen Jessica Van , Duggal Neil
Published: December 2014

Objective:

Optimal fusion technique and peri-operative management of patients undergoing anterior cervical discectomy (ACD) is unclear.We document current practice patterns among Canadian spinal surgeons regarding the surgical management of single level degenerative cervical spondylosis.

Methods:

We conducted a web-based survey of neurosurgeons and spinal orthopedic surgeons in Canada. We asked questions pertaining to the management of single level cervical degenerative disc disease causing radiculopathy and/or myelopathy, including frequency of fusion following single-level discectomy, preferred fusion technique, indications and frequency of use of anterior plating, and use of an external cervical orthosis following surgery. Demographic factors assessed included training background, type and length of practice.

Results:

Sixty respondents indicated that their practice involved at least 5% spine surgery and were included in further analysis. Neurosurgeons comprised 59% of respondents, and orthopedic surgeons 41%. Fusion was employed 93% of the time following ACD; autologous bone was the preferred fusion material, used in 76% of cases. Neurosurgeons employed anterior cervical plates in 42% of anterior cervical discectomy and fusion cases, whereas orthopedic surgeons used them 70% of the time. External cervical orthoses were recommended for 92% of patients without plates and 61% of patients with plates. Surgeons who had been in practice for less than five years were most likely to be performing spinal surgery, using anterior cervical plates, and recommending the postoperative use of cervical orthoses.

Conclusion:

Practice patterns vary among Canadian surgeons, although nearly all employ fusion and many use instrumentation for single-level ACD. Training background, and type and length of practice influence practice habits.
The Vibration Quantitation Scale (VQS): A Simple, Reproducible Bedside Measure of Sensory Function in Multiple Sclerosis
Authors: Carter J. , Wasser T. , Statler S. , Rae-Grant A.D.
Published: December 2014

Objectives:

To assess the utility of a bedside measure of sensation (the Vibration Quantitation Scale (VQS)) in patients with multiple sclerosis (MS) and in normal controls. To correlate the VQS with the Kurtzke Expanded Disability Severity Score (EDSS) and sensory abnormalities in these patients.

Methods:

We developed the VQS and tested its performance in patients with MS of various ages, MS types, and EDSS scores. We compared this with controls (normal volunteers or patients with other neurological diseases) who did not have sensory symptoms. In a subgroup, two examiners measured VQS independently at the same patient visit. Astandard C-128 tuning fork was used for the VQS measurement.

Results:

The VQS had a good inter-observer reproducibility (r=0.920, p<0.001). The VQS fell with increasing age in normals consistent with declining sensory function. The VQS was significantly lower in the multiple sclerosis patients compared with age - matched controls (p<0.001). Abnormalities in VQS were present in patients with brief duration of MS (<5 years) and low EDSS scores, correlating with the presence of sensory abnormalities early in the disease course in some patients. There was a strong correlation between the VQS and EDSS (r=-0.509). The VQS correlated with abnormal sensation in the hands (r=0.310), but did not meet statistical significance for abnormal sensation in the feet or face. Asecond cohort of MS patients was studied using a modified VQS measure (single stimulation, omitting forehead measurement). This reconfirmed the correlation between the modified VQS and EDSS as well as with age. The modified VQS may be useful in clinical practice since it takes little time and is strongly correlated with the EDSS (r=0.578).

Conclusion:

The VQS provides a continuous sensory scale applicable in most patients with MS, which is measurable with standard bedside equipment, and which may avoid some of the pitfalls of sensory scoring in MS.
Synchronous Lumbar Disc Herniation in Adult Twins. Case Report
Authors: Bhardwaj Ratan , Midha Rajiv
Published: December 2014

Objective:

To report an unusual case of large synchronous lumbar disc herniation in adult twins.

Methods:

Case report and relevant literature review.

Results:

The authors report a case of adult female monozygotic twins who synchronously presented with huge lumbar disc herniation. Rather than being a curious coincidence, this case highlights the potential importance of hereditary factors in the causation of lumbar disc degeneration. The relevant literature regarding the role of genetic factors and their relationship to other risk factors in lumbar disc degeneration is reviewed and discussed.

Conclusion:

Synchronous lumbar disc herniation in adult twins is a rare event. It, however, sheds light on the role of genetic factors in disc degeneration.
Pulmonary Edema and Cardiac Dysfunction Following Subarachnoid Hemorrhage
Authors: McLaughlin Nancy , Bojanowski Michel W. , Girard François , Denault André
Published: December 2014

Background:

Pulmonary edema (PE) can occur in the early or late period following subarachnoid hemorrhage (SAH). The incidence of each type of PE is unknown and the association with ventricular dysfunction, both systolic and diastolic, has not been described.

Methods:

Retrospective chart review of 178 consecutive patients with SAH surgically treated over a three-year period. Patients with pulmonary edema diagnosed by a radiologist were included. Early onset SAH was defined as occurring within 12 hours. Cardiac function at the time of the PE was analyzed using hemodynamic and echocardiographic criteria of systolic and diastolic dysfunction. Pulmonary edema was observed in 42 patients (28.8%) and was more often delayed (89.4%). Evidence of cardiac involvement during PE varied between 40 to 100%.

Results and conclusions:

Pulmonary edema occurs in 28.8% of patients after SAH, and is most commonly delayed. Cardiac dysfunction, both systolic and diastolic, is commonly observed during SAH and could contribute to the genesis of PE after SAH.
Outcome after Stroke upon Awakening
Authors: Nadeau Janel O. , Fang Jiming , Kapral Moira K. , Silver Frank L. , Hill Michael D.
Published: December 2014

Background:

An estimated 20-25% of all strokes occur during sleep and these patients wake up with their deficits. This study evaluated outcomes among patients who woke up with stroke compared to those who were awake at stroke onset.

Methods:

Using data from the Registry of the Canadian Stroke Network Phases 1 and 2, we compared demographics, clinical data and six-month outcomes between patients with stroke-on-awakening versus stroke-while-awake. Strokes of all types (ischemic stroke, transient ischemic attack, intracerebral hemorrhage and subarachnoid hemorrhage) were included. Standard descriptive statistics, multivariable logistic regression and general linear modeling were applied to the data to compare variables.

Results:

Among 2,585 stroke patients, 349 (13.5%) woke up with stroke and 2,236 (86.5%) did not. Patients with stroke-on-awakening were more likely to have higher blood pressure and to suffer ischemic stroke, but stroke severity, measured by level of consciousness, did not differ. Mortality both at discharge and at six-month follow-up did not differ between the two cohorts. However, patients with stroke-on-awakening were less likely to return home, and their median Stroke Impact Scale-16 scores were 7.0 points lower compared to those with stroke-while-awake.

Conclusions:

There are minor demographic and clinical differences between patients with stroke-on-awakening and stroke-while-awake. Functional outcomes are slightly worse among patients with stroke-on-awakening, an effect which was driven by poor outcomes among patients with subarachnoid hemorrhage.
Hyaline Body Myopathy: Adulthood Manifestations
Authors: Rafay Mubeen F. , Halliday William , Bril Vera
Published: December 2014

Background:

Hyaline body myopathy (HBM) is a rare chronic nonprogressive congenital myopathy, with variable patterns of inheritance.

Methods:

We describe a patient with congenital HBM with progression of weakness and increasing muscle pain in adulthood. Three muscle biopsies, done at various times in her life, are reported.

Results:

Symptoms started during childhood; however, as an adult, following a period of stability with no progression of the disease, the patient became symptomatic with worsening proximal limb weakness, severe aching pain and hypertrophy of calves. Moderate elevations of serum creatine kinase and myopathic features were noted on electrophysiologic testing. Muscle pathology showed significant fatty infiltration of skeletal muscle and increased number of fibers with internal nuclei. Histology demonstrated the presence of subsarcolemmal, well-delineated hyaline areas, which on histochemical studies was shown to be limited to type1 fibers. The hyaline bodies were dark with pH 4.2 ATPase and with immunohistochemical studies reacted only with myosin heavy chain slow. Electron microscopy showed the hyaline bodies to be composed of nonmembrane bound, fairly even sized granular material, which merged with the adjacent myofibrils. Earlier muscle biopsies, done during childhood, also revealed presence of similar subsarcolemmal hyaline deposits.

Conclusion:

There appears to be a pattern of presentation with adulthood progression in HBM, which has not been described before. Further case studies are required to understand the clinical progression in HBM.
Methadone in the Management of Intractable Neuropathic Noncancer Pain
Authors: Moulin D. E. , Palma D. , Watling C. , Schulz V.
Published: December 2014

Objective:

To evaluate the role of methadone in the management of intractable neuropathic noncancer pain.

Methods:

A case series of 50 consecutive noncancer pain patients who were seen at a tertiary care centre and treated with oral methadone for a variety of intractable neuropathic pain states.

Results:

The mean age was 52.7 years and the mean duration of follow-up was 13.9 months. Post-discectomy nerve root fibrosis, complex regional pain syndrome, peripheral neuropathy and central spinal cord pain syndromes were the most common diagnoses. Over 90% had been treated with one or more tricyclic antidepressants and anticonvulsants and a similar number had received other adjuvant analgesics. All patients had failed treatment with one or more conventional opioid analgesics (mean 2.8) at a mean maximal morphine dose of 384 mg (or equivalents) per day. Twelve patients had failed spinal cord stimulation. Nineteen patients (38%) did not tolerate initial methadone titration or thought their pain was worse on methadone. Five patients (10%) declared initial benefit but required repetitive dose escalation and eventually became non-responders. Twenty-six patients (52%) reported mild (4), moderate (15), marked (6) or complete (1) pain relief and continued on methadone at a mean maintenance dose of 159.8 mg/day for a mean duration of 21.3 months. Fourteen patients (28%) reported improved function on methadone relative to previous treatments.

Conclusions:

Methadone appears to have unique properties including N-methyl-D-aspartate antagonist activity that may make it especially useful in the management of intractable neuropathic pain. This observation needs to be tested in randomized, controlled trials.
Progress in Clinical Neurosciences: Measuring the Benefit of Therapies for Neurological Disorders
Authors: Bussière Miguel , Wiebe Samuel
Published: December 2014

Background:

Clinicians in the neurosciences need to interpret and apply a growing body of evidence about therapy.

Methods:

Using a clinical scenario about painful diabetic neuropathy and evidence about one treatment option, we review the advantages, limitations, and the clinical interpretation of commonly reported measures of effectiveness, emphasizing their application to the care of individual patients.

Results:

Absolute differences between treatment and control groups (e.g., absolute risk difference) are clinically intuitive and preferable to relative measures (e.g., relative risk). The number needed to treat is particularly useful and clinically applicable. Continuous measures are best interpreted using thresholds of clinically important change, which provide information about the number of patients experiencing meaningful improvement or worsening.

Conclusions:

Using simple principles of evidence based care, clinicians can correctly interpret the common measures of treatment effectiveness and apply them to the care of individual patients.
Hereditary Ataxia, Spastic Paraparesis and Neuropathy in the French-Canadian Population
Authors: Dupré Nicolas , Bouchard Jean-Pierre , Brais Bernard , Rouleau Guy A.
Published: December 2014

Historical events have shaped the various regional gene pools of the French-Canadian (FC) population, leading to increased prevalence of some rare diseases. The first studies of these founder effects were performed in large part by astute clinicians such as André Barbeau. In collaboration with others, he contributed greatly to the delineation of phenotypic subtypes of these conditions. As such, the following neurogenetic disorders were first identified in patients of FC origin: AOA2, ARSACS, HSAN2, RAB, and HMSN/ACC. We have summarized our current knowledge of the main hereditary ataxias, spastic parapareses and neuropathies that are particular to the FC population. The initial genetic characterization of the more common and homogeneous of these diseases has been largely completed. We predict that the regional populations of Canada will allow the identification of new rare forms of hereditary ataxias, spastic parapareses and neuropathies, and contribute to the unravelling of the genetic basis of these entities.
Radiosurgical Retreatment for Brain Arteriovenous Malformation
Authors: Mirza-Aghazadeh Javad , Andrade-Souza Yuri M. , Zadeh Gelareh , Scora Daryl , Tsao May N. , Schwartz Michael L.
Published: December 2014

Objective:

To analyze our experience with a second radiosurgical treatment for brain arteriovenous malformations (BAVMs) after an unsuccessful first radiosurgical treatment.

Methods:

Between 1993 and 2000, 242 patients were treated by the Toronto Sunnybrook Regional Cancer Center using a LINAC system. Fifteen of these patients required a second radiosurgical intervention due to the failure of the first procedure. Data was collected on baseline patient characteristics, BAVM features, radiosurgery treatment plan and outcomes. Brain arteriovenous malformation obliteration was determined by follow-up MRI and angiography and the obliteration prediction index (OPI) calculated according to a previously established formula.

Results:

The median interval between the first and second treatment was 46 months (range 39-109). The median follow-up after the second procedure was 39 months (range 26 to 72). The mean BAVM volume before the first treatment was 8.9cm3 (range 0.3-21) and before the second treatment was 3.6cm3 (range 0.2-11.6). The mean marginal dose during the first treatment was 18Gy (range 12-25) and during the second treatment was 16Gy (range 12-20). After the second treatment, nine patients had obliteration of their BAVM confirmed by angiography and one patient had obliteration confirmed by MRI, resulting in an obliteration rate of 66.6%, which is very comparable to that predicted by the OPI (65%). After the second treatment two patients had a radiation-induced complication (13.3%).

Conclusion:

Retreatment of BAVM using a second radiosurgery procedure is a safe and effective option that offers the same rate of success as the initial radiosurgery and an acceptable risk of radiation-induced complication.
A Case of Familial Creutzfeldt-Jakob Disease Presenting with Dry Cough
Authors: Larue Sandrine , Verreault Steve , Gould Peter , Coulthart Michael B. , Bergeron Catherine , Dupré Nicolas
Published: December 2014

Background:

Clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is based on the classical triad of rapidly progressive dementia, myoclonus and abnormal EEG. The 200k mutation within the gene encodingPrP, located on the short arm of chromosome 20, accounts for more than 70% of families with CJD worldwide.

Case Report:

Herein, we report a patient who developed persistent dry cough and classical signs of CJD, including severe cognitive decline, cerebellar signs, and myoclonic jerks, leading to death a few weeks after disease onset. Mutation screening showed that he had the 200k point mutation in thePRNPgene. His mother had died twenty years earlier with neuropathologically confirmed CJD. She had presented a rapidly progressive ataxia with myoclonus, dementia, visual hallucinations, and the same persistent dry cough.

Conclusions:

The clinical presentation of this familial CJD case with persistent dry cough is quite unusual. Therefore, a neurological etiology should be sought when confronted with an unexplained persistent cough.
Canadian Association of Neurosciences Review: Polyglutamine Expansion Neurodegenerative Diseases
Authors: Truant Ray , Raymond Lynn A. , Xia Jianrun , Pinchev Deborah , Burtnik Anjee , Atwal Randy Singh
Published: December 2014

Since the early 1990s, DNA triplet repeat expansions have been found to be the cause in an ever increasing number of genetic neurologic diseases. A subset of this large family of genetic diseases has the expansion of a CAG DNA triplet in the open reading frame of a coding exon. The result of this DNA expansion is the expression of expanded glutamine amino acid repeat tracts in the affected proteins, leading to the term, Polyglutamine Diseases, which is applied to this sub-family of diseases. To date, nine distinct genes are known to be linked to polyglutamine diseases, including Huntington's disease, Machado-Joseph Disease and spinobulbar muscular atrophy or Kennedy's disease. Most of the polyglutamine diseases are characterized clinically as spinocerebellar ataxias. Here we discuss recent successes and advancements in polyglutamine disease research, comparing these different diseases with a common genetic flaw at the level of molecular biology and early drug design for a family of diseases where many new research tools for these genetic disorders have been developed. Polyglutamine disease research has successfully used interdisciplinary collaborative efforts, informative multiple mouse genetic models and advanced tools of pharmaceutical industry research to potentially serve as the prototype model of therapeutic research and development for rare neurodegenerative diseases.
Convergence Paralysis as a Manifestation of Polyarteritis Nodosa
Authors: Wylie Jessica , Campbell Craig , Pope Janet , Akikusa Jonathan , Laxer Ronald M. , Nicolle Dave
Published: December 2014

Polyarteritis nodosa (PAN) is a rare, systemic necrotizing vasculitis of medium-sized arteries. The American College of Rheumatology criteria for the diagnosis of PAN includes at least three of: 1. weight loss < 4 kg, 2. livedo reticularis, 3. testicular pain or tenderness, 4. myalgias, weakness or leg tenderness, 5. mono-or polyneuropathy, 6. diastolic hypertension, 7. elevated blood creatinine or urea, 8. hepatitis B antigen or antibody in the serum, 9. aneurysms or occlusions of visceral arteries or 10. granulocytes on small or medium sized artery biopsy. Common sites of involvement include skin, joints, kidneys, gastrointestinal tract and peripheral nerves. Central nervous system involvement has been reported in up to 40% of cases; the usual manifestations are encephalopathy, focal deficits and seizures. Descriptions of PAN in the pediatric literature has been reported in fewer than 250 children.
Canadian Drug Regulatory Framework
Authors: Kelly L. , Lazzaro M. , Petersen C.
Published: December 2014

The role of regulatory drug submission evaluators in Canada is to critically assess both the data submitted and the sponsor's interpretation of the data in order to reach an evidence-, and context- based recommendation as to the potential benefits and potential harms (i.e., risks) associated with taking the drug under the proposed conditions of use. The purpose of this document is to outline the regulatory framework in which this assessment occurs, including: defining what “authorization to market a drug in Canada” means, in terms of the role of the sponsor, the responsibility of Health Canada in applying the Food and Drugs Act prior to and after marketing authorization, and the distinction between regulatory authorization versus physician authorization; highlighting organizational, process and legal factors within Health Canada related to authorization of clinical trials and authorization to market a drug; considerations during the review process, such as regulatory and scientific issues related to the drug, patient populations and trial designs; application of international guidelines, and decisions from other jurisdictions; regulatory realities regarding drug authorization, including the requirement for wording in the Product Monograph to accurately reflect the information currently available on the safe and effective use of a drug, and that hypothesis-confirming studies are essential to regulatory endorsement; current issues related to the review of therapies for dementia, such as assessing preventative treatments, and therapies that have symptomatic versus disease-modifying effects, statistical issues regarding missing data, and trial design issues.
Target Symptoms and Outcome Measures: Cognition
Authors: Kirk Andrew
Published: December 2014

The Cognitive section of the Alzheimer's Disease Assessment Scale (ADAS-Cog) remains the most widely used cognitive measure in dementia trials although it does not assess attention, executive function, or agnosia. Designed for use in Alzheimer's disease (AD), it may not be ideal in assessing patients with other diagnoses. The ADAS-Cog differentiates between AD patients, patients with Mild Cognitive Impairment, and normal controls. It has been used in trials of drugs for vascular and mixed dementia and dementia with Lewy bodies. It is not clear that the ADAS-Cog is adequate for assessing cognition in frontotemporal dementia. Well-validated aphasia batteries, such as the Western Aphasia Battery, can be used to assess language. Brief tests of frontal function such as the Frontal Assessment Battery or the Executive Interview might be useful additions in frontotemporal dementia trials. The most widely used assessment tool for patients with advanced dementia is the Severe Impairment Battery. The domains tested are analogous to those assessed by the ADAS-Cog. The Mini-Mental State Exam and the Modified Mini-Mental State Examination are useful in stratifying patients for trial entry. Cognitive measures better tailored to the diseases in question are needed for non-Alzheimer dementias.
Treatment of Moderate to Severe Alzheimer's Disease: Rationale and Trial Design
Authors: Herrmann Nathan
Published: December 2014

Moderate to severe Alzheimer's disease (AD) is characterized by increasing cognitive, functional, and behavioural dysfunction that results in increased caregiver burden and, eventually, complete dependence. Despite its significance as a societal health problem, there are few treatment trials of cognitive enhancers or disease modifying agents for this stage of illness. Studies suggest the cholinesterase inhibitors, especially donepezil, may provide benefit. Several studies provide support for the use of the NMDA receptor antagonist memantine as monotherapy or added to a cholinesterase inhibitor for moderate to severe AD. While there are no published guidelines for the treatment of moderate to severe AD, these studies do provide guidance for recommendations for study design and outcome measures. Such studies are urgently needed.
Clinical Trials in Parkinson's Disease Dementia and Dementia with Lewy Bodies
Authors: Camicioli Richard , Gauthier Serge
Published: December 2014

Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) are pathological overlapping and important causes of dementia for which clinical trials are in their infancy. Cholinesterase inhibitors may be of benefit in DLB and PDD, as suggested by placebo-controlled clinical trials of rivastigmine and donepezil. The anti-psychotic agent clozapine has been of benefit in PD and PDD, but other agents, such as quetiapine, require adequate assessment. Barriers to trials include pathological overlap that can lead to inaccuracies in clinical diagnosis, unavailability of a consensus definition for PDD, unanswered questions regarding natural history and the paucity of validated outcome measures. Motor impairment must be considered in patients with PDD and DLB; conversely, cognitive impairment should be assessed in trials targeting motor impairment in advanced PD. Potential targets for treatment include onset of dementia, cognitive impairment, behavioral impairment, functional decline, falls, nursing home placement, mortality, quality of life and economic impact. Biomarkers including neuroimaging and cerebrospinal fluid markers are not currently established. At present PDD and DLB are distinct entities by definition. Future studies, including clinical trials and biomarker studies, will help to further define the clinical and therapeutic implications of this distinction.
Frontotemporal Dementia: Recommendations for Therapeutic Studies, Designs, and Approaches
Authors: Freedman Morris
Published: December 2014

Frontotemporal dementia (FTD) is one of three neurobehavioural syndromes produced by frontotemporal lobar degeneration. Despite the importance of FTD as a cause of dementia, especially in younger age groups, and a rationale for therapies targeting serotonergic and dopaminergic systems, there have been no large scale treatment trials in FTD. Moreover, there is no consensus on standards to facilitate comparison across therapeutic trials. This paper reviews the literature on therapeutic trials in FTD and outlines general recommendations for standards related to the development of future treatment studies in this disorder. Drugs tested in FTD include trazodone, galantamine, idazoxan, lithium plus fluoxetine, lithium plus paroxetine, SSRIs, l-deprenyl, moclobemide, methylphenidate, piracetam, rivastigmine, donepezil, olanzapine, risperidone, amantadine, guanfacine, allopurinol, and bromocriptine. Improvement has been reported in FTD for all drugs except piracetam, guanfacine and galantamine, although there was improvement on galantamine in primary progressive aphasia. Whereas improvement has been reported for paroxetine and other SSRIs, as well as idazoxan and methylphenidate, paroxetine and idazoxan have also been reported to cause a decline in function, and a marginally significant decline has been reported for methylphenidate. In addition, patients with Pick's disease, which is part of the spectrum of frontotemporal lobar degeneration, showed improvement on calcium EDTA. Six studies are double-blind placebo-controlled trials: two reports of cases using idazoxan and group trials using trazodone, paroxetine, galantamine and methylphenidate. It is recommended that experts in FTD arrive at a consensus to define standards for all clinical trials in FTD. These should include standards for diagnostic criteria, tests of severity, experimental design, and outcome measures.