bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular characterization of endolithic cyanobacteria inhabiting exposed dolomite in central Switzerland
Authors: Sigler William V. , Bachofen Reinhard , Zeyer Josef
Published: June 2003

The phototrophic microbial community inhabiting exposed dolomite in the alpine Piora Valley (Switzerland) forms a distinct endolithic bilayer that features adjacent red dolomite (exterior) and green dolomite (interior) layers that are c. 0.5–1 mm below the rock surface. Characterization of the community, with an emphasis on cyanobacteria, was conducted with culture‐dependent and ‐independent approaches. Direct microscopy of green dolomite revealed four distinct morphotypes consistent with Chlorophyta genera Chlorella and Stichococcus and the Cyanobacterial genera Nostoc and Calothrix, whereas only Stichococcus and Nostoc were observed in the red dolomite. Enrichment in BG‐11 media resulted in the growth of Chlorella and Stichococcus. Denaturing gradient gel electrophoresis (DGGE) analysis of DNA extracted from the enrichment revealed two dominant phylotypes with sequence similarity to Chlorella osrokiniana chloroplast and the cyanobacteria genus Leptolyngbya. 16S rRNA gene‐based DGGE analysis of DNA extracted directly from both layers indicated that although both layers harboured phylotypes most similar to the Cyanobacterial genera Nostoc, Chroococcidiopsis, and Microcoleus, and the Chlorophyte Stichococcus bacillaris, the two layers also harboured unique genera such as Scytonema, and Symploca (red, external layer of dolomite) and Chlorella (green, internal layer of dolomite). The unique community structure of each layer suggests a selection process directed by the pressures of the endolithic environment. We conclude that the overall composition of the phototrophic community closely resembles that of endolithic communities located in extreme habitats, suggesting that a cosmopolitan community inhabits this defined niche.
Jeff Schell
Authors: Verstraete W.
Published: June 2003

Jeff Schell, a pioneer and leading figure in Ti plasmid‐induced tumour formation in plants, and in plant genetic engineering, died on 17 April 2003. His early days in Ghent, and the exciting discoveries about Ti plasmids, are related here by his colleagues from the Ghent University
Peri‐operative radiotherapy for rectal cancer: the case for a selective pre‐operative approach – the third way
Authors: Crawshaw A. , Hennigan T. , Smedley F. H. , Leslie M. D.
Published: June 2003

Peri‐operative radiotherapy has been used widely in addition to surgery in an attempt to reduce local recurrence (LR) following surgical resection of rectal cancer. Currently different groups follow different approaches with some routinely administering one weeks pre‐operative radiotherapy to all cases of operable mobile cancer with others favouring postoperative chemoradiotherapy for selected high risk groups. In this review we bring together the changes in surgery, pathology and imaging that have occurred in recent years and together with the data from recent randomized pre‐operative radiotherapy trials propose a logical and optimal way of managing rectal cancer. This third way is selective and pre‐operative and should ensure a low rate of LR with radiotherapy reserved for those cases that need it.
Thrombosis complicating high dose intravenous immunoglobulin: report of three cases and review of the literature
Authors: Zaidan R. , Moallem M. Al , Wani B. A. , Shameena A. R. , Tahan A. R. Al , Daif A. K. , Rajeh S. Al
Published: June 2003

High dose intravenous immunoglobulin (IVG) is increasingly used in a broad range of immune mediated diseases. Thrombosis was exceptionaly reported as a complication of this therapy. We describe three cases of thrombotic complications during or soon after IVIG treatment: myocardial infarction in a man and cerebral infarctions in an elderly man, associated with peripheral ischemia in a woman. In addition we review the published cases in the literature and discuss the possible etiologic factors.
Magnetoencephalography in stroke: a 1‐year follow‐up study
Authors: Gallien P. , Aghulon C. , Durufle A. , Petrilli S. , De Crouy A. C. , Carsin M. , Toulouse P.
Published: June 2003

Recovery after stroke is closely linked to cerebral plasticity. Magnetoencephalography (MEG) is a non‐invasive technique, which allows location of cerebral cells activities. In the present work, a cohort of patients has been studied with MEG. Twelve patients with a recent ischemic or hemorragic stroke were included as soon as possible after onset of stroke. Neurologic assessment, including standard neurologic examination, functional independence measure (FIM) and Orgogozo's scale was performed for 1 year in addition to a study of the somatosensory evoked field (SEF) using a 37‐channel Biomagnetometer system. No response could be recorded in five patients at the first SEF exploration. In three cases, no response was ever recorded during the study. All these patients had a bad recovery. The location of the SEF sources was always in the normal non‐infarcted cortex of the postcentral gyrus. Sensory recovery seemed to be linked to the reorganization of the persistent functional cortex, which was a limiting factor for recovery. These observations confirm the experimental results obtained in animal models. After stroke it can be assumed that in the case of incomplete lesion, an intensive sensory peripheral stimulation could maximize the use of residual sensory function and then contribute to improve the sensory deficit. In case of total sensory loss other techniques have to be used, such as visual monitoring of hand activity in order to improve hand function.
Acute carotid obliteration: a new vascular manifestation in POEMS syndrome
Authors: Erro M. E. , Lacruz F. , Aymerich N. , Ayuso T. , Soriano G. , Gállego J. , Villanueva J. A.
Published: June 2003

The case of a 65‐year‐old woman with polyneuropathy, organomegaly, skin changes and monoclonal gammopathy of IgG‐lambda type is described. This patient developed an acute carotid obliteration during oral anticoagulation and despite absence of vascular risk factors. Macroangiopathy has been described as a rare systemic manifestation of POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal spike and skin changes), affecting the coronary and lower limbs arteries. To our knowledge, this is the second case of POEMS syndrome with a cerebrovascular manifestation.
Development of teaching and tuition in the specialty of neurology in the Netherlands
Authors: Keyser A.
Published: June 2003

After a short survey of the early history of neurology and psychiatry in the Netherlands, the development of the specialty of neurology is discussed. During the 20th century the training of neurologists and the certification of specialists evolved from an informal master‐fellow organization towards a strongly reglemented and legally based procedure. A nationwide Specialist Registration Commission supervises the quality of the training of specialists. Registered neurologists in the Netherlands are subject to a re‐certification programme that controls the requirements to be fulfilled by the specialists such as their active involvement in patient care (for at least 16 h a week), attendance of the annual postgraduate courses in neurology (5‐year cycle) and regular participation in international congresses of neurology. The undergraduate training in neurology, the neurology clerkship and the postgraduate training in neurosciences are described. Measures taken in order to maintain the balance between the supply of and the demand for neurological care in the near future are reported.
Subcortical aphasia: three different language disorder syndromes?
Authors: Kuljic‐Obradovic D. C.
Published: June 2003

The study analyses clinical presentation of language functions of 32 patients with subcortical aphasia induced by stroke. The patients have been divided into three groups according to neuroanatomic localization of the lesion, defined by CT and MRI examination (striato‐capsular aphasia, aphasia associated with white matter paraventricular lesions and thalamic aphasia). The following batteries and tests were used: the neurologic examination, CT scan, MRI, Doppler ultrasound, Mini Mental State Examination, Boston Diagnostic Aphasia Examination (BDAE), Boston Naming Test (BNT), Token Test and Verbal Fluency Test. Clinical presentation of subcortical aphasias is characterized with preserved repetition, however, some groups differ by certain specific features of language impairment. Striato‐capsular aphasia and aphasia associated with white matter paraventricular lesions are characterized with lack of speech fluency, occurrence of literary paraphasias, mainly preserved comprehension and naming. Thalamic aphasia, however, is characterized with fluent output, impaired comprehension and naming with predominant verbal paraphasias. The specific features of language impairment suggest that subcortical structures contribute to language organization. Considering the results of language tests we presume that the most prominent feature in striato‐capsular aphasia is phonetic impairment of language, opposite to thalamic aphasia where lexical‐sematic processing seems to be affected.
Evidence of an association between Chlamydia pneumoniae and cerebrovascular accidents
Authors: Bucurescu G. , Stieritz D. D.
Published: June 2003

The authors report results of a retrospective pilot study showing a strong association between patients with stroke/TIA and the presence of circulating IgG and IgA antibodies to Chlamydia pneumoniae. These results support the hypothesis that chronic active or persistent infection may play a role in the mechanism of thrombosis. The risk for stroke associated with Chlamydial circulating antibodies appeared to be independent of other risk factors such as diabetes and hypercholesterolemia.
The quality of acute stroke units on a nation‐wide level: the Austrian Stroke Registry for acute stroke units
Authors: Steiner M. M. , Brainin M. ,   for the participants in the Austrian Stroke Registry for Acute Stroke Units
Published: June 2003

Concepts for stroke units that cover the acute phase vary. Therefore, the network of acute stroke units that is being set up in Austria in a uniform way is of general interest. This nationwide network has been established in accordance to evidence‐based recommendations and prespecified criteria for available resources. The location for such a unit follows a maximum of 90‐min isochrones (transport time) to the hospital. The quality of the network is currently documented and the results are reported.

A nationwide stroke registry was prospectively performed on 15 stroke units that were already functional in this network. The aim was to document the quality performance of Austrian stroke units, focusing on rapid admissions, ready availability of investigations and therapies performed. Outcome measures were Barthel scale, Rankin score and percentages of complications.

Between August 1998 and December 2000, 2313 patients with ischemic stroke or with primary intracerebral hemorrhage admitted to an Austrian stroke unit within 24 h after onset of symptoms were prospectively included. Forty‐three percent of the patients had a moderate or severe stroke. Fifty‐seven percent of all patients were admitted to the stroke unit within 3 h after the onset of symptoms. Twenty‐seven percent of these patients were brought in by ambulance accompanied by an emergency physician. Two percent of patients were admitted by helicopter. Fifty‐four percent of patients had their first brain imaging within 30 min after admission, another 26% within 3 h. Intravenous thrombolysis was performed in 4.1% of patients. The overall stroke‐unit mortality was about 6.8% and mortality at 3 months was 12.9%. The outcome at 3 months showed a modified Rankin Scale score of 0 or 1 in 47% of patients, denoting none or mild impairment.

This network of acute stroke units is highly efficient in terms of rapid admissions, short intrahospital delays, as well as rapid use of readily available investigations. Stroke units seem to be well accepted by the general public and the medical community because our data show that all types of strokes are treated in Austrian stroke units, including severe strokes. The total number of concurrently treated acute strokes in other institutions across Austria is not known and no formal comparison with other systems of hospitalized care was undertaken, therefore further research is necessary.
Intracortical inhibition and facilitation are impaired in patients with early Parkinson's disease: a paired TMS study
Authors: Bareš M. , Kaňovský P. , Klajblová H. , Rektor I.
Published: June 2003

Twelve patients with early Parkinson's disease (PD), none of whom had received any previous l‐DOPA treatment, but using other antiparkinsonian drugs, were studied using transcranial magnetic stimulation (TMS). Contralateral and ipsilateral hemispheres were examined, with a focus on the more pronounced parkinsonian symptoms. The conditioning‐test TMS paradigm (with a subthreshold conditioning stimulus and a suprathreshold test stimulus) was used through a stimulating round coil. Paired stimuli of short (3, 5 and 7 ms), medium (10, 15 and 20 ms), and long (100, 150, 200 and 250 ms) interstimulus intervals (ISI) were pseudo‐randomly mixed with a single stimulus. The first interosseus muscle was used for the motor‐evoked potential recordings. Ten healthy subjects (age and sex matched) were studied in the same manner to obtain normative data. When both groups were compared, the significant difference (reduction of the intracortical inhibition and facilitation) between the PD patients and the control group was found at the short and the medium ISI (3, 5, 7, 10, 15 and 20 ms) in both hemispheres (P < 0.05). The longer ISI produced non‐significant differences between the two groups in intracortical excitability. There was a non‐significant difference in the motor threshold. In conclusion, it can be supposed that both intracortical inhibition and facilitation are impaired in patients with early PD using other antiparkinsonian treatments than l‐DOPA or dopamine agonists.
Characterization of freezing of gait subtypes and the response of each to levodopa in Parkinson's disease
Authors: Schaafsma J. D. , Balash Y. , Gurevich T. , Bartels A. L. , Hausdorff J. M. , Giladi N.
Published: June 2003

To assess the effect of levodopa on distinct freezing of gait (FOG) subtypes in patients with ‘off’ FOG. Nineteen patients (12 men, mean age 62.0 ± 8.4 years) with Parkinson's disease and clinically significant FOG during ‘off’ states were videotaped whilst walking 130 m during ‘off’ and ‘on’ states. Three independent observers characterized the type, duration, and clinical manifestations and quantified FOG by analyzing the videotapes. Their combined mean scores were used for statistical analysis. The intra‐class correlation coefficient assessed inter‐observer reliability. Wilcoxon and Friedman tests evaluated differences in mean frequencies of FOG characteristics. During ‘off’ states, FOG was elicited by turns (63%), starts (23%), walking through narrow spaces (12%) and reaching destinations (9%). These respective values were only 14, 4, 2 and 1% during ‘on’ states (P < 0.011). Moving forward with very small steps and leg trembling in place were the most common manifestations of FOG; total akinesia was rare. Most FOG episodes took <10 s and tended to be shorter during ‘on’ states. Levodopa significantly decreased FOG frequency (P < 0.0001) and the number of episodes with akinesia (P < 0.001). Distinction amongst FOG subtypes enables evaluation of distinctive therapeutic response. Levodopa helps in reducing the frequency and duration of ‘off’‐related FOG.
Pramipexole and pergolide in the treatment of depression in Parkinson's disease: a national multicentre prospective randomized study
Authors: Rektorová I. , Rektor I. , Bareš M. , Dostál V. , Ehler E. , Fanfrdlová Z. , Fiedler J. , Klajblová H. , Kulišt’ák P. , Ressner P. , Svátová J. , Urbánek K. , Velísková J.
Published: June 2003

An 8‐month multicentre prospective randomized study aimed at comparing the effects of dopamine receptor agonists pramipexole (PPX; Mirapexin®) and pergolide (PRG; Permax®) as add‐on to L‐dopa therapy on depression [Montgomery and Asberg Depression Rating Scale (MADRS)] in 41 non‐demented patients (25 men, 16 women) suffering from both mild or moderate depression and advanced Parkinson's disease (PD). The assessment was performed by a blinded independent observer. Motor symptoms (UPDRS III), motor complications (UPDRS IV), activities of daily living (UPDRS II and VI) and depressive symptoms as measured by Self – Rating Depression Scale by Zung were evaluated in an open‐label design.

The average value of Zung scores decreased significantly in both groups with no statistical difference between both groups. A significant decrease in the average value of MADRS scores was present only in the PPX group. The average UPDRS scores decreased significantly with no statistical difference between both groups at the comparable average total daily dose of both preparations. In both cases, the total daily dose of L‐dopa decreased significantly but the decrease was statistically more pronounced in the PRG group.

Our results demonstrate the antidepressant effect of PPX in patients with PD while we can't make any conclusions with regard to antidepressant effect of PRG.
Post‐polio syndrome and total health status in a prospective hospital study
Authors: Farbu E , Rekand T , Gilhus N. E.
Published: June 2003

New loss of function among patients with previous polio is frequently reported and has several causes. All patients referred to the Department of Neurology, Haukeland University Hospital, Bergen, for 13 months during 2000–2001 with diagnosis late effects of polio were examined prospectively to identify their symptoms and loss of function. Eighty‐five patients aged 47–91 years with mean of 61 years were included. The most common complaints were pain (44%), muscular weakness (27%), and fatigue (16%). Muscular weakness occurred in lower limbs in 75%, in respiratory muscles in only 5%. Walking in stairs was impaired in 72% and outdoor walking in 65%. Seventeen patients (19%) reported no loss of function.

Post‐polio syndrome was diagnosed in 26% of the patients. Polio‐related loss of function including cervical and lumbosacral radiculopathies, mononeuropathies and degenerative joint disease were found in an additional 53%. Eleven patients (13%) had distinct non‐polio‐related disorders that caused new loss of function. The remaining 8% had a stable condition. In conclusion, the majority of polio patients who seek hospital, experience a new loss of function because of polio‐related disorders. A careful neurological examination is necessary to identify the correct diagnosis and treatment.
Pure quadriceps myopathy in two sisters
Authors: Mahjneh I. , Somer H. , Paetau A. , Marconi G.
Published: June 2003

The authors carried out a clinical, laboratory and muscle computed tomographgy CT follow‐up study of 18–21 years on two sisters affected by quadriceps myopathy (QM). The onset in the fourth decade was a weakness in the thighs. During the follow‐up study, the patients showed only vasti muscles involvement, normal creatine kinase (CK) levels, myopathic muscle biopsy and electromyography (EMG) and normal membrane protein expression on immunocytochemical analysis. Therefore, all muscle pathologies known to have quadriceps involvement as a leading feature have been ruled out. We conclude that our patients have pure QM with probable autosomal recessive inheritance.
Botulinum toxin in the management of childhood muscle spasticity: comparison of clinical practice of 17 treatment centres
Authors: Bakheit A. M. O.
Published: June 2003

At least two randomized controlled trials (RCTs) have shown botulinum toxin type A (BtxA) to be efficacious and safe when used in the management of muscle spasticity in children. However, the need to use standard treatment protocols in these studies obscures some aspects of routine clinical practice that may have important effect on clinical outcomes. The purpose of this study was to seek additional information on the use of BtxA that is not usually captured by RCTs. This was performed by reviewing the clinical practice of practitioners in 17 treatment centres in Europe. The details of treatment with BtxA, including the dose, site and frequency of injections and the use of anaesthesia or sedation, were abstracted from the patient's records. Information was also obtained on the response to treatment and the occurrence and severity of adverse events. The data on 758 children who received a total of 1594 treatments in 17 different clinics in Europe were analysed. Ninety‐four per cent of patients had cerebral palsy. There was a general agreement on the indications for treatment but the average dose of BtxA used varied between centres. One treatment centre used general anaesthesia (GA) prior to injections in most patients. The reported efficacy and adverse events profile was similar for all centres. The evidence from routine clinical practice for the efficacy and safety of BtxA in the management of muscle spasticity in children, as described in this study, is in agreement with that of most of the open‐label and RCTs published to date. The present study also demonstrates the disagreement between clinicians on the optimal dose of BtxA for individual muscles and confirms that the injections can be carried out without GA in almost all cases.
Increased risk of migraine with typical aura in probands with familial hemiplegic migraine and their relatives
Authors: Thomsen L. L. , Olesen J. , Russell M. B.
Published: June 2003

We investigated the occurrence of migraine without aura (MO) and migraine with typical aura (MA) amongst probands with familial hemiplegic migraine (FHM) and their first degree relatives in order to evaluate the relations between these syndromes. A total of 44 FHM probands and 240 first degree relatives were identified in the Danish population. The pattern of familial aggregation was assessed by population relative risk (PRR) calculations. Amongst FHM probands the PRR of MO was 1.5 (95% CI: 0.8–2.2), whereas the PRR of MA was 7.1 (95% CI: 5.0–9.2). Thus, compared with the general population, FHM probands had no increased risk of MO but a significantly increased risk of MA. A similar pattern was seen amongst their first degree relatives, who had no increased risk of MO, whereas the risk of MA was significantly increased; 7.6 times in FHM‐affected first degree relatives and 2.4‐times in non‐FHM‐affected first degree relatives. These results are contrary to a sharing of genetic mechanisms between FHM and MO. Furthermore, they suggest that the genetic abnormality causing FHM may also cause attacks with the symptomatology of MA.
Striatal infarcts mimicking frontotemporal dementia: a case report
Authors: Nishio Y. , Nakano Y. , Matsumoto K. , Hashimoto M. , Kazui H. , Hirono N. , Ishii K. , Mori E.
Published: June 2003

We described a patient with bilateral striatal infarcts, in whom stereotyped and disinhibited behaviors were insidiously emerged over 2 years mimicking frontotemporal dementia (FTD). A positron emission tomography with 18‐fluorodeoxy glucose showed a hypometabolism in the frontal lobes, basal ganglia, and thalami. The peculiar behavioral alterations remained unchanged for the following 7 years, suggesting that the disease is not degenerative but of vascular origin. A disruption of the fronto‐subcortical circuits at the level of the striatum or the anterior thalamic peduncle is attributable to the FTD‐like behavioral and cognitive syndrome.
Predicting spontaneous early neurological recovery after acute ischemic stroke
Authors: Arboix Adrià , García‐Eroles Lluis , Comes Emili , Oliveres Montserrat , Balcells Miquel , Pacheco Gustavo , Targa Cecilia
Published: June 2003

We assessed predictors of spontaneous early neurological recovery after acute ischemic stroke by means of multivariate analysis in a cohort of 1473 consecutive patients treated at one academic center. At hospital discharge, spontaneous neurological improvement or good outcome was defined as grades 0–2 of the Rankin scale, and poor outcome (no improvement or in‐hospital death) as grades 3–5. Spontaneous recovery of neurological deficit at the time of discharge from the hospital was observed in 16% of patients with cerebral infarction (n = 238). Dysarthria‐clumsy hand syndrome improved in 44% of patients and was the only variable significantly associated with in‐hospital functional recovery in three logistic regression models that in addition to lacunar syndromes, included demographic variables, cardiovascular risk factors, and clinical variables [odds ratio (OR) 2.56], neuroimaging findings (OR 2.48), and outcome data (OR 2.39), respectively. Clinical factors related to severity of infarction available at stroke onset have a predominant influence upon in‐hospital outcome and may help clinicians to assess prognosis more accurately. Our work gives a contribution into prognostic factors after acute ischemic stroke. With regard to patterns of stroke, dysarthria‐clumsy hand syndrome was a significant predictor of spontaneous in‐hospital recovery in ischemic stroke patients.
Clinical warning criteria in evaluation by computed tomography the secondary neurological headaches in adults
Authors: Aygun D. , Bildik F.
Published: June 2003

Our aims were to investigate the frequency of intracranial lesions detected by cranial computed tomography (CT‐scan) amongst adult patients who had clinical warning criteria (CWC) for secondary neurological headaches and to determine the importance of CWC in predicting a possible lesion on CT‐scan. Seventy consecutive patients with headache exhibiting CWC were included in this prospective study. The CWC included: (i) increase in the intensity and frequency of headache; (ii) abrupt onset of headache; (iii) persistence of headache despite analgesics; (iv) alteration of the characteristics of headache; and (v) presence of focal neurological symptoms or findings. The mean age of the patients was 46.5 years; the female‐to‐male ratio was 1.5. Of the patients, 35.7% had a neurological cause identified by CT‐scan, and 64.3% had normal CT‐scan. In the patients without lesion, of headaches, 64.4% were primary, and 35.6% were from undefined headache group. Although, of the above criteria, only the 5th was different markedly in the patients with lesion than the patients without lesion, in evaluation by CT‐scan the secondary neurological headaches in adults, all CWC should look for absolutely in their history and physical examination.
Neurovascular territory involved in different etiological subtypes of ischemic stroke in the Perugia Stroke Registry
Authors: Paciaroni M. , Silvestrelli G. , Caso V. , Corea F. , Venti M. , Milia P. , Tambasco N. , Parnetti L. , Gallai V.
Published: June 2003

We studied the correlation between the potential causes of stroke (TOAST etiological groups) and the involvement of different vascular territories seen on computed tomography (CT) scans in patients with ischemic stroke. Information from consecutive patients with a first‐ever stroke have been prospectively coded and entered into a computerized data bank (Perugia Stroke Registry). A population of 1719 patients were evaluated: 1284 patients (74.7%) had ischemic stroke. Large artery disease was the main cause of entire middle cerebral artery (MCA) territory infarcts (40.9%), superficial MCA territory infarcts (35.7%), and watershed infarcts (68.2%). The highest presence of emboligenic heart disease was found in the entire MCA territory infarcts (28.8%) or superficial (29.4%) supratentorial infarcts and in cerebellar infarcts (36.8%). Small artery disease was the most common presumed cause of deep MCA infarcts (75.0%) and posterior cerebral artery (PCA) territory infarcts (52.1%). In conclusion: stroke location could depend on its etiology. Lacunar infarcts are the most prevalent (36.7%), being mostly localized in the deep MCA territory; large artery disease includes more than two‐thirds of watershed infarcts; the most prevalent territories involved in cardioembolic stroke are the entire MCA and posterior fossa.
Seizure Suppression by Adenosine A1 Receptor Activation in a Mouse Model of Pharmacoresistant Epilepsy
Authors: Gouder Nicolette , Fritschy Jean‐Marc , Boison Detlev
Published: June 2003

Summary:  Purpose: Because of the high incidence of pharmacoresistance in the treatment of epilepsy (20–30%), alternative treatment strategies are needed. Recently a proof‐of‐principle for a new therapeutic approach was established by the intraventricular delivery of adenosine released from implants of engineered cells. Adenosine‐releasing implants were found to be effective in seizure suppression in a rat model of temporal lobe epilepsy. In the present study, activation of the adenosine system was applied as a possible treatment for pharmacoresistant epilepsy.

Methods: A mouse model for drug‐resistant mesial temporal lobe epilepsy was used, in which recurrent spontaneous seizure activity was induced by a single intrahippocampal injection of kainic acid (KA; 200 ng in 50 nl).

Results: After injection of the selective adenosine A1‐receptor agonist, 2‐chloro‐N6‐cyclopentyladenosine (CCPA; either 1.5 or 3 mg/kg, i.p.), epileptic discharges determined in EEG recordings were completely suppressed for a period of ≤3.5 h after the injections. Seizure suppression was maintained when 8‐sulfophenyltheophylline (8‐SPT), a non–brain‐permeable adenosine‐receptor antagonist, was coinjected systemically with CCPA. In contrast, systemic injection of carbamazepine or vehicle alone did not alter the seizure pattern.

Conclusions: This study demonstrates that activation of central adenosine A1 receptors leads to the suppression of seizure activity in a mouse model of drug‐resistant epilepsy. We conclude that the local delivery of adenosine into the brain is likely to be effective in the control of intractable seizures.
Vigabatrin, but not Gabapentin or Topiramate, Produces Concentration‐related Effects on Enzymes and Intermediates of the GABA Shunt in Rat Brain and Retina
Authors: Sills Graeme J. , Butler Elaine , Forrest Gerard , Ratnaraj Neville , Patsalos Philip N. , Brodie Martin J.
Published: June 2003

Summary:  Purpose: The antiepileptic drug (AED) vigabatrin (VGB), which exerts its pharmacologic effects on the γ‐aminobutyric acid (GABA) system, causes concentric visual field constriction in >40% of exposed adults. This may be a class effect of all agents with GABA‐related mechanisms of action. We compared the concentration‐related effects of VGB in rat brain and eye with those of gabapentin (GBP) and topiramate (TPM), both of which have been reported to elevate brain GABA concentrations in humans.

Methods: Adult male rats (n = 10) were administered 0.9% saline (control), VGB (250, 500, 1,000 mg/kg), GBP (50, 100, 200 mg/kg), or TPM (12.5, 25, 50, 100 mg/kg). At 2 h after dosing, animals were killed, a blood sample obtained, the brain dissected into eight distinct regions, and the retina and vitreous humor isolated from each eye. Samples were analyzed for several GABA‐related neurochemical parameters, and serum and tissue drug concentrations determined.

Results: VGB treatment produced a significant (p < 0.05) dose‐related increase in GABA concentrations and decrease in GABA‐transaminase activity in all tissues investigated. This effect was most pronounced in the retina, where VGB concentrations were 18.5‐fold higher than those in brain. In contrast, GBP and TPM were without effect on any of the neurochemical parameters investigated and did not accumulate appreciably in the retina.

Conclusions: These findings corroborate a previously reported accumulation of VGB in the retina, which may be responsible for the visual field constriction observed clinically. This phenomenon does not appear to extend to other GABAergic drugs, suggesting that these agents might not cause visual field defects.
Wada Memory Performance Predicts Seizure Outcome after Epilepsy Surgery in Children
Authors: Lee Gregory P. , Park Yong D. , Westerveld Michael , Hempel Ann , Blackburn Lynn B. , Loring David W.
Published: June 2003

Summary:  Purpose: Wada memory asymmetries were examined in children from four comprehensive epilepsy surgery centers who subsequently underwent epilepsy surgery to determine whether Wada memory performance could predict degree of seizure relief in children.

Methods: One hundred fifty‐six children (between ages 5 and 16 years) with intractable epilepsy underwent Wada testing before resective epilepsy surgery (93 within the left hemisphere, and 63 within the right hemisphere). Memory stimuli were presented soon after intracarotid amobarbital injection, and recognition memory for the items was assessed after return to neurologic baseline. Eighty‐eight children underwent unilateral temporal lobe resection, and 68 had extratemporal lobe resections. One hundred four (67%) children were seizure free (Engel class I), and 52 (33%) were not seizure free (Engel classes II–IV) at follow‐up (mean follow‐up interval, 2.3 years).

Results: Seizure‐free children recalled 19.3% more Wada memory items after ipsilateral injection than did non–seizure‐free children (p = 0.008). If analysis was restricted to youngsters with temporal lobectomies (TLs), seizure‐free children recalled 27.7% more items after ipsilateral injection than did non–seizure‐free TL children (p = 0.004). With regard to individual patient prediction, 75% of children who had memory score asymmetries consistent with the seizure focus were seizure free. In contrast, only 56% of children whose memory score asymmetries were inconsistent with the seizure focus were seizure free (p = 0.01).

Conclusions: Results suggest that Wada memory performance asymmetries are related to the degree of seizure relief after epilepsy surgery in children and adolescents.
TsTx Toxin Isolated from Tityus serrulatus Scorpion Venom Induces Spontaneous Recurrent Seizures and Mossy Fiber Sprouting
Authors: Regina Maria , Sandoval Lopes , Lebrun Ivo
Published: June 2003

Summary:  Purpose: To characterize the long‐term behavioral, electroencephalographic (EEG) and histopathologic features after a single TsTx microinjection into the hippocampus of rats.

Methods: TsTx, 2 μg, or 1 μl of 0.1 M phosphate buffer was injected into the right dorsal hippocampus of the rat. EEG records and behavioral observations were made over a period of 10 h after injection. For a period of 4 months, the animals were observed for the occurrence of convulsive seizures. At the end of the experiment, the brains were processed by the neo‐Timm and Nissl methods.

Results: After intrahippocampal TsTx injection, three distinct phases were observed: (a) an immediate period that lasted 1 day, during which the motor and electrographic seizures characteristic of status epilepticus (SE) were seen; (b) a silent period (31–49 days), characterized by normal EEG and behavior; and (c) a period of spontaneous recurrent seizures (SRSs). The seizure frequency was one to two per week. Four months after TsTx injection, hippocampal neuronal loss and mossy fiber sprouting in the supragranular layer of the dentate gyrus were observed.

Conclusions: The SRSs observed in this study may be associated with the TsTx‐induced SE and brain damage. All animals injected with the toxin showed massive pyramidal neuronal loss in the dorsal hippocampus as well as intense gliosis and atrophy. Mossy fiber sprouting in the supragranular layer of the dentate gyrus was observed in those animals that had SRSs. The effects observed may be due, at least in part, to TsTx‐enhanced release of glutamate in hippocampal pathways.
Transient Hypohidrosis Induced by Topiramate
Authors: De Carolis Piero , Magnifico Fabiola , Pierangeli Giulia , Rinaldi Rita , Galeotti Massimo , Cevoli *Sabina , Cortelli Pietro
Published: June 2003

Summary:  Purpose: Hypohidrosis during topiramate (TPM) treatment was recently reported in children. We describe an adult epilepsy patient who developed inability to sweat as well as heat intolerance while undergoing treatment with TPM.

Methods: To detect the site of the sweat block, patient underwent examination of sweat gland function, cardiovascular autonomic test, and body temperature rhythm determination.

Results: During TPM treatment, cardiovascular autonomic function and circadian rhythm of body core temperature were normal, whereas thermoregulatory sweat test (TST) showed anhydrosis. This adverse drug effect was quickly resolved after drug discontinuation.

Conclusions: Because of normal cardiovascular autonomic function and central and peripheral thermoregulatory mechanisms, we hypothesize that hypohidrosis during TPM treatment could be due to a carbonic anhydrases (CA) block at the level of sweat gland.
Effects of Seizure Repetition on Postictal and Interictal Neurocardiac Regulation in the Rat
Authors: Naritoku Dean K. , Casebeer Doris J. , Darbin Olivier
Published: June 2003

Summary:  Purpose: Human epilepsy is associated with abnormalities in cardiac regulation, as measured by reductions of heart rate variability (HRV) and approximate entropy (ApEn), but it is not known how these abnormalities are related to seizure experience.

Methods: Baseline electrocardiogram (ECG) was recorded from seizure‐naive rats. They were subjected daily to maximal electroshock (MES), which induced tonic seizures with hindlimb extension, for a total of 10 days. ECG was obtained for 30 min before and after the first and last seizure. R‐R variability, spectral variability, and ApEn were calculated to determine changes in pre‐ and postictal cardiac regulation. Before the last seizure, interictal parameters were compared with baseline values to determine changes in interictal HRV as a consequence of seizure repetition. Postictal values obtained after the last seizure were compared with the initial postictal data to look for changes in postictal cardiac regulation.

Results: During the postictal state, a mild, but significant, loss of ApEn was present after either the first or last seizure. Seizure repetition induced loss of R‐R variability and high‐frequency spectral band, which was present both interictally and postictally.

Conclusions: The results suggest that convulsive seizures are associated with an immediate reduction of the complexity of cardiac rhythm regulation, as reflected by reductions of ApEn. Seizure repetition may induce long‐term neural abnormalities in neurocardiac regulatory systems, especially parasympathetic, which limit appropriate autonomic responses. These acquired abnormalities may, in turn, predispose individuals to cardiac arrhythmia and sudden unexpected death in epilepsy.
Spectroscopic Metabolic Abnormalities in mTLE with and without MRI Evidence for Mesial Temporal Sclerosis Using Hippocampal Short‐TE MRSI
Authors: Mueller Susanne G. , Laxer Kenneth D. , Suhy Joyce , Lopez Ria C. , Flenniken Derek L. , Weiner Michael W.
Published: June 2003

Summary:  Purpose: Long echo time (TE) spectroscopy reliably identifies the epileptogenic hippocampus in mesial temporal lobe epilepsy. Short‐TE spectroscopy gives additional metabolic information but may have more artifacts. The aim of this study was to test (a) lateralization of the seizure focus by short‐TE spectroscopy, and (b) value of myoinositol (MI) in the identification of the epileptogenic hippocampus.

Methods: Twenty‐four patients with temporal lobe epilepsy: 16 with mesial temporal sclerosis (TLE‐MTS), eight patients with normal magnetic resonance imaging (MRI; TLE‐No), and 16 controls were studied with hippocampal 2D short‐TE magnetic resonance spectroscopic imaging (MRSI).

Results: In TLE‐MTS, the ipsilateral N‐acetylaspartate (NAA) was decreased compared with contralateral (p = 0.03) or controls (p = 0.007). Additionally, the ipsilateral MI was decreased compared with controls (p = 0.012). TLE‐No values showed no side differences and were not different from controls. Abnormalities in the anterior hippocampus correctly lateralized the epileptogenic hippocampus in ≤82% of TLE‐MTS and in ≤80% of the TLE‐No.

Conclusions: The accuracy of short‐TE MRSI at 1.5 T for focus lateralization in mTLE is comparable to that of long‐TE MRSI. MI might be helpful for focus lateralization, but more information about the factors influencing the MI concentration is needed.
Absence Epilepsy with Onset before Age Three Years: A Heterogeneous and Often Severe Condition
Authors: Chaix Yves , Daquin Géraldine , Monteiro Franklin , Villeneuve Nathalie , Laguitton Virginie , Genton Pierre
Published: June 2003

Summary:  Purpose: The classification of epilepsies and epileptic syndromes recognizes three syndromes with typical absences [TA, i.e., childhood and juvenile absence epilepsies (CAE and JAE), and epilepsy with myoclonic absences (EMA), none of which is characterized by onset in early childhood]. Although several other forms of absence epilepsies have been described recently, none concerns infants and very young children, and little is known about the nosology and prognosis of early‐onset absences.

Methods: We retrospectively selected all cases with onset of absences as the only or major seizure type before age 3 years and ≥2 years of follow‐up among cases newly referred between 1986 and 2002. Neurospychological assessments (generally IQ measure), behavior patterns, and schooling situations were reviewed for each child.

Results: We found 10 patients (7 F, 3 M). No child had sensory or motor deficits: neuroimaging was performed in nine and was normal in eight, with aspecfic findings in one. Only two could be characterized as CAE and EMA, respectively, both with seizure control and a good cognitive outcome. Among the remaining eight cases, four had a fairly homogeneous presentation with predominantly brief absences and clearly asymmetric interictal EEGs. All eight had neuropsychological and/or behavioral difficulties. Three had full seizure control, and five, persisting absences, with a follow‐up ranging beetween 2 years 8 months to 9 years 4 months; only one child was older than 12 years.

Conclusions: Great heterogeneity exists among absence epilepsies of early onset, which are rare conditions. Only a few patients can be categorized into well‐known syndromes. The overall prognosis is poor. Early onset of absences is uncommon, and multicenter studies should help clarify the nosology and prognosis.
Cysticercosis as a Major Risk Factor for Epilepsy in Burundi, East Africa
Authors: Nsengiyumva Georges , Druet‐Cabanac Michel , Ramanankandrasana Bienvenue , Bouteille Bernard , Nsizabira Léopold , Preux Pierre‐Marie
Published: June 2003

Summary:  Purpose: Human cysticercosis is a direct consequence of infection by Taenia solium larvae (Cysticercus cellulosae). Results of studies on the impact of neurocysticercosis on epilepsy in Africa are inconsistent. The objective was to evaluate the role of cysticercosis in epilepsy in Burundi.

Methods: A prevalent matched case–control design was used in the Kiremba area, Burundi, between March and April 2001. One case with epilepsy was matched to two control subjects, according to their age. Cases were subjects who had shown at least two unprovoked epileptic seizures within a 24‐h time range and who lived in the Kiremba area. The control subjects also lived in Kiremba and had neither neurologic illness nor kinship with the people with epilepsy. Seropositivity for cysticercosis was the exposure variable. Three hundred twenty‐four prevalent cases, with onset of epilepsy between 1950 and 2000, and 648 age‐matched controls were included.

Results: This study found a link between cysticercosis infestation and the occurrence of epilepsy (odds ratio, 3.8; 95% confidence interval, 2.5–5.1).

Conclusions: The study highlighted the importance of cysticercosis in the area of Kiremba, as 31.5% of the control subjects screened positive for this parasite. The attributable risk for cysticercosis was 50% (95% confidence interval, 42–57) in this population.
Effects of Vagus Nerve Stimulation on Sleep‐related Breathing in Epilepsy Patients
Authors: Marzec Mary , Edwards Jonathan , Sagher Oren , Fromes Gail , Malow Beth A.
Published: June 2003

Summary:  Purpose: To describe the effects of vagus nerve stimulation (VNS) on sleep‐related breathing in a sample of 16 epilepsy patients.

Methods: Sixteen adults with medically refractory epilepsy (nine men, seven women, ages 21–58 years) underwent baseline polysomnograms (PSGs). Three months after VNS therapy was initiated, PSGs were repeated. In addition, patient 7 had a study with esophageal pressure monitoring, and patient 1 had a continuous positive airway pressure (CPAP) trial.

Results: Baseline PSGs: One of 16 patients had an apnea–hypopnea index (AHI) >5 (6.8). Treatment PSGs: Five of 16 patients had treatment AHIs >5. Respiratory events were more frequent during periods with VNS activation (on‐time) than without VNS activation (off‐time; p = 0.016). Follow‐up studies: Esophageal pressure monitoring in patient 7 showed crescendos in esophageal pressure during VNS activation, supporting an obstructive pattern. The CPAP trial of patient 1 showed that all respiratory events were associated with VNS stimulation at low CPAP levels. They were resolved at higher CPAP levels.

Conclusions: Treatment with VNS affects respiration during sleep and should be used with care, particularly in patients with preexisting obstructive sleep apnea. The AHI after VNS treatment remained <5 in the majority of patients and was only mildly elevated (<12) in five patients. In one patient, CPAP resolved VNS‐related respiratory events.
Hypothalamic Hamartoma and Seizures: A Treatable Epileptic Encephalopathy
Authors: Berkovic Samuel F. , Arzimanoglou Alexis , Kuzniecky Ruben , Harvey A. Simon , Palmini Andre , Andermann Frederick
Published: June 2003

Summary: Hypothalamic hamartomas may be associated with gelastic seizures, focal seizures, and a generalized epileptic encephalopathy, with severe seizures and cognitive and behavior decline. Despite earlier views to the contrary, good evidence now exists that all these clinical features are caused, directly or indirectly, by the hamartoma. Resection of these lesions was long regarded as too hazardous and unlikely to benefit seizure control. It is now clear that hypothalamic hamartomas can be effectively treated with a variety of surgical approaches with sustained seizure control and often seizure freedom. Qualitative observations suggest that behavior and cognition also improve with treatment, but quantitative validation is required. The specific approach should be tailored according to the surgical anatomy of the lesion and the experience of the surgeon. Choices include a transcallosal approach (good for intraventricular lesions), a pterional approach (useful for interpeduncular lesions), a transventricular endoscopic approach, or destruction of the lesion with radiofrequency probes or gamma knife radiosurgery. The previously dismal outlook for children with severe seizures associated with this lesion has now dramatically changed. These insights may have implications for other epileptic encephalopathies of childhood.