Weight gain has been recognized as a common adverse effect of valproic acid (VPA) that leads to discontinuation in some patients but its incidence and correlates have been rarely studied.

We have analyzed the records retrospectively and interviewed 70 adult patients attending an epilepsy clinic on VPA mono- or polytherapy followed over a median of 27 months (range 3-189), as well as 20 patients on carbamazepine (CBZ) monotherapy. Patients were divided into non-weight gainers (< 5% baseline body weight), mild-moderate weight gainers (5-10% body weight) and marked weight gainers (> 10% body weight). The following variables were statistically analyzed to determine their relationship to weight gain: gender, age, body mass index, drug dose, personal or family history of obesity and monotherapy versus polytherapy.

Seventy-one percent of the VPA group were weight gainers versus 43% in the CBZ group. A weight gain of more than 4 kg in 70% of the VPA group was observed. The weight gain was often sustained and frequently socially significant to the patients. Patients below or within normal range body mass index prior to the start of VPA experienced the most severe percentage weight gain. From the structured patient interviews, patients with no personal history of weight problems experienced the greatest initial weight increase.

Strategies should be devised to help patients avoid weight gain when starting on VPA, especially if they are not already overweight.

The Saguenay-Lac-Saint-Jean (SLSJ) region is a geographically isolated area (population 285,955) located in the Northeastern part of the Province of Quebec, Canada. Using a population-based register, the genealogical reconstruction of 502 individuals with ruptured intracranial aneurysm (RIA) showed a familial aggregation (the presence of aneurysm in two or more first- to third-degree relatives) for 144 (28.7%) of them; this proportion is much higher than reported elsewhere.

In order to assess the genetic predisposition to RIA in the SLSJ population, the objective of the present study is to compare familial and non-familial cases and to provide an estimate of the recurrence risk ratio for siblings.

The age at the time of rupture, the number of intracranial aneurysms for each patient and the location of RIAs were not statistically different in the familial versus the non-familial group. Of the 3449 siblings, 20 (0.58%) had suffered a RIA. The recurrence risk ratio calculated for siblings (defined as the risk of disease among siblings divided by the estimated population prevalence) is 1.6 (CI 95% 1.0 - 2.4). In other respects, we observed very large kinships in the SLSJ population, with an average number of siblings of 7.2 (SD ± 3.4), ranging from 0 to 17 individuals. With such large families and on the basis of chance alone, we expected 31.3% of the patients to have at least one first- to third-degree relative with RIA.

These data show that siblings of patients with RIA in the SLSJ population have a greater risk of RIA than the general population. Nevertheless, the largest part of the familial occurrence observed in the SLSJ region can be explained by accidental aggregation, due to large kinships. We propose that, in this population, an underlying genetic predisposition must be suspected only when three or more cases of RIA are identified among first- to third-degree relatives.

We previously showed that Manitoba Hutterites seek physician care for varicella zoster virus infection significantly less than non-Hutterites. The current study was undertaken to measure varicella zoster virus seroprevalence for Hutterite and non-Hutterite controls.

Blood was obtained from 315 Hutterites and 259 similar age and sex controls at the time of blood donations to The Canadian Red Cross Society. The controls were from the same or a contiguous postal code area and were collected at the same time as the Hutterite samples. The immune status of the specimens was determined by the ELISA method (enzyme linked immunosorbent assay).

Twenty-eight per cent of 315 Hutterites had no immunity and an additional 25% had only marginal immunity. Among the 259 controls, 10% had no immunity and an additional 10% had only marginal immunity (p < .0001).

Manitoba Hutterites have significantly decreased seroprevalence to varicella zoster virus infection. This study of serum varicella zoster virus antibodies verifies a previous population based study that demonstrated the relative rarity of varicella and herpes zoster among a particular population group.

Difficulty recalling people's names is common in the adult population, especially in the elderly. The subject is scarcely mentioned in the literature. An 82-year-old patient gave the history that for 33 years he had made prospective observations on his own difficulty with people's names.

Documentation and analysis of the patient's personal observations in which his ability to recall the names of friends, acquaintances, colleagues, public figures, movie stars and athletes is compared with that of his spouse. A suitable test-battery for the names of famous North American persons was not available.

The patient's capability in recalling people's names was clearly inferior to that of his spouse. The patient's intellect was otherwise intact and the impairment seemed to be isolated to the category of proper-naming. Doubts were raised about the patient's own conclusion that the deficit was progressive.

A parallel may be drawn between benign difficulty recalling people's names and the acquired categorical deficit for proper naming reported in the literature in recent years. Based on Damasio's concept of anatomically compartmentalized sensory subsystems, it is hypothesized that our patient's symptom represents an innate limited capacity for proper naming.

We tested the efficacy and safety of linopirdine, a novel phenylindolinone, in the treatment of Alzheimer's disease.

A multicentre, randomized, double-blind, parallel group, placebo-controlled trial of linopirdine (30 mg three times per day or placebo). Patients (n = 382, 55% male, 98% Caucasian, age range 51-95 years) with mild or moderate Alzheimer's disease, of whom 375 received at least one treatment dose were analysed. There were no important differences between the groups at baseline.

No difference was seen in Clinical Global Impression scores between patients receiving placebo and those receiving linopirdine (n = 189). Small differences in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores were seen throughout the study favouring linopirdine; at 6 months the ADAS-Cog scores were 20.2 (linopirdine) and 22.1 (placebo) p = 0.01.

This trial did not detect clinically meaningful differences in patients receiving linopirdine for 6 months, despite evidence of a small degree of improved cognitive function. Further studies may benefit from more sensitive tests of treatment effects in Alzheimer's disease.

To investigate the mechanisms underlying disability in multiple sclerosis (MS), 40 patients with the relapsing-remitting form of the disease and 13 patients with secondary progressive MS underwent multimodal evoked potential (EP), motor evoked potential (MEP), and spinal motor conduction time evaluation. Clinical disability was evaluated by the expanded disability status scale (EDSS) and functional system scales. In secondary progressive MS patients, magnetic resonance imaging (MRI) was used to obtain a semiquantitative estimate of the total lesion load of the brain.

Spinal motor conduction time was significantly longer in secondary progressive MS patients than controls (p < 0.001) and relapsing-remitting MS patients (p < 0.05), but did not differ between relapsing-remitting patients and controls. Spinal motor conduction times also correlated directly with EDSS scores (p < 0.001) and pyramidal functional system scores (p < 0.001). Brain lesion load (4960.3 ± 3719.0 mm2) and the total number of lesions (67.7 ± 37.0) in secondary progressive MS did not correlate with disability scores. For the following EPs, the frequencies of abnormalities were significantly higher in secondary progressive MS patients than relapsing-remitting patients: visual evoked potentials (p < 0.05), somatosensory evoked potentials and upper limb motor evoked potentials (p < 0.01), and brainstem auditory evoked potentials, lower limb somatosensory evoked potentials and lower limb motor evoked potentials (p < 0.001).

These findings suggest that disability in secondary progressive MS patients is mainly due to progressive involvement of corticospinal tract in the spinal cord.

Transtentorial herniation of large cerebral fragments is a rare phenomenon.

Case Study

Examination of the brain of a 35-year-old male showed massive intracerebral hemorrhage resulting in displacement of basal ganglia components into the fourth ventricle.

Sufficiently rapid intracerebral bleeding can dissect fragments of cerebrum and displace them long distances across the tentorial opening.

Skin rashes are a well known complication of antiepileptic drug (AED) treatment. It has also been recognized that some patients will develop rashes from multiple AEDs (cross sensitivity). There are very few studies that have attempted to determine the frequency of cross sensitivity among AEDs.

Charts of all patients attending an epilepsy outpatient clinic were reviewed to determine AED exposure and the occurrence of a rash from AEDs.

633 patients had 1,875 exposures to 14 AEDs. Rashes occurred from carbamazepine (N = 27), phenytoin ( N = 21), phenobarbital (N = 5) and lamotrigine (N = 1). A rash from 2 or more AEDs occurred in 14 patients and involved predominantly carbamazepine and phenytoin. Among the patients exposed to both phenytoin and carbamazepine 10/17 (58%) of patients with a rash from phenytoin also had a rash from carbamazepine; conversely 10/25 (40%) patients with a carbamazepine rash also had a rash from phenytoin. 4/5 patients with a phenobarbital rash were sensitive to carbamazepine and/or phenytoin. Amongst the other most commonly used AEDs no rashes occurred from valproic acid or clobazam.

The cross sensitivity rate for rashes involving carbamazepine and phenytoin is 40-58%. If a rash develops from either of these AEDs, valproate or clobazam are safe alternatives.

The most common cause of acromegaly is excess of growth hormone (GH) secretion.

We report a 42-year-old male patient, who had become acromegalic over the past 5 years. There were no visual changes or change in sexual function, no gynaecomastia or galactorrhoea. Both CT and MRI scans showed a large mass measuring 2.5 x 2.5 x 3.5 cm, originating from the sella turcica and extending into and totally filling up the sphenoid sinus with diffusely invasive features.

Basal serum GH level was within normal range, but insulin-like growth factor 1 (IGF-1) was elevated with slightly increased prolactin (PRL) and impaired GH secretory regulation as well. A pituitary adenoma was partially removed through transsphenoidal microsurgery. Pathology confirmed a mammo-somatotrophic adenoma but immunocytochemistry study of the tumour showed only positivity for PRL but not GH.

When acromegaly occurs without GH level elevation, one should pay attention that: 1) IGF-1 might be the cause of the clinical feature of acromegaly; 2) The tumour might undergo morphological transformation; and 3) Hyperinsulinemia or GH receptor antibody formation could also be the cause of the acromegalic appearance.

Patients with carpal tunnel syndrome (CTS) sometimes report sensory symptoms outside the median nerve distribution. This study was designed to provide a more detailed assessment of these symptoms.

Patients with clinical suspicion of upper limb neuromuscular lesions were divided into those with electrodiagnostic (EDX) evidence of CTS, and those without. CTS patients with superimposed nerve abnormalities were excluded. Motor and sensory symptoms were assessed in the exclusive CTS patients.

Over 50% of patients with exclusive CTS reported tingling or numbness over the whole hand, ulnar or radial nerve distributions. Some patients reported symptoms proximal to the wrist. Sensory signs did not extend beyond the median nerve distribution. Numbness and nocturnal pain were predictive of positive EDX evidence of CTS.

Sensory symptoms outside the distribution of the median nerve are common in CTS. For enhanced sensitivity in diagnosis it is useful to be aware of these “atypical” symptoms. Reports of numbness and nocturnal pain are strong indicators of CTS.

Pituitary dysfunction caused by intracranial aneurysms is rare. We report a patient with the unique feature of hyperprolactinemia to a degree previously seen only with prolactinsecreting tumours.

Case report.

A 42-year-old woman had a galactorrhea, left-sided headache, reduced vision in the left eye and a left temporal hemianopsia. Serum prolactin was elevated (365 μg/L). Cranial computed tomography (CT) revealed a suprasellar mass, which carotid angiography showed to be a left internal carotid artery aneurysm. At craniotomy, this aneurysm and a smaller one of the ophthalmic artery were repaired, and the patient's vision returned to normal. The prolactin level fell to normal. Follow-up CT showed no evidence of pituitary adenoma or hypothalamic lesion.

Carotid aneurysm can cause reversible pituitary dysfunction. A prolactin level >300 μg/L is not a reliable cut-off for distinguishing prolactin-secreting adenomas from other causes of elevated prolactin. A co-existing prolactinoma was felt to be ruled out by both a normal CT scan and normal prolactin levels following aneurysm repair. Patients with marked hyperprolactinemia should be considered for angiography or MRI to rule out carotid aneurysm, since the consequences of pituitary exploration in this setting are potentially grave.

Orthochromatic leukodystrophy with pigmented glia and scavenger cells is a rare leukodystrophy of unknown etiology. This report describes a 42-year-old man with a history of depression, dementia and parkinsonism having the pathological features of orthochromatic leukodystrophy with pigmented glia.

We reviewed the clinical history and pathology of autopsy and brain biopsy material.

Imaging revealed bilateral cerebral white matter hypodensities. At autopsy, the brain demonstrated a leukodystrophy affecting predominantly the cerebral hemispheres and characterized by demyelination, and cytoplasmic pigment deposits in oligodendroglia and astrocytes. The pigment had the staining properties of ceroid-lipofuschin and on ultrastructural examination was composed of membrane-bound lipid and electron-dense inclusions which had a fingerprint-like pattern. Similar pigment inclusions were not observed on ultrastructural examination of renal, splenic or hepatic tissue obtained at autopsy. The brain biopsy contained cerebral cortex with sparse subcortical white matter in which a few oligodendroglia and fewer astrocytes at the grey/white junctions showed cytoplasmic pigmentary inclusions identical to those described above. However, due to the paucity of white matter in the specimen a definite diagnosis of orthochromatic leukodystrophy with pigmented glia was not made.

The diagnosis of orthochromatic leukodystrophy with pigmented glia and scavenger cells can only be made antemortem if the brain biopsy contains adequate white matter and although a rare condition, it should be considered in the differential diagnosis of an adult onset leukodystrophy.

Lumbosacral plexopathy is a complication of diabetes mellitus. Conn's syndrome from an aldosterone secreting adenoma may be associated with hypokalemia and rhabdomyolysis but mild hyperglycemia also usually occurs.

Case description.

A 70-year-old male diagnosed as having Conn's syndrome, hypokalemia and mild hyperglycemia developed rhabdomyolysis and lumbar plexopathy as a presenting feature of his hyperaldosteronism. His rhadbdomyolysis rapidly cleared following correction of hypokalemia but recovery from the plexopathy occurred slowly over several months. Definite resection of the aldosterone secreting adenomas reversed the hyperglycemia.

Our patient developed lumbar plexopathy resembling that associated with diabetes mellitus despite the presence of only mild and transient hyperglycemia.

Spontaneous dissection of the vertebral artery is uncommon.

Case study.

We report a 49-year-old woman who presented with the rapidly progressing basilar artery syndrome who was given an intravenous dose of tissue plasminogen activator seven hours after the onset of first symptoms. Thirty minutes after the injection, a dramatic recovery of the patient's consciousness and neurological signs was noted.

To our knowledge, this is the first reported case of intravenous tissue plasminogen activator use in acute vertebral artery dissection.

CSF shunting procedures are generally considered the fundamental therapy of syphilitic hydrocephalus.

We followed up with CSF analysis and MR imaging a patient with progressive mental and gait disturbances and tetraventricular hydrocephalus due to tertiary syphilis who was treated for 14 days with high dose intravenous penicillin alone.

Clinical and CSF abnormalities resolved within a few months, whereas the hydrocephalus disappeared only 30 months after therapy.

Before consideration of a CSF shunting procedure, a trial of high dose intravenous penicillin is warranted for patients with syphilitic hydrocephalus.

Lhermitte-Duclos disease (LDD) is a rare pathologic entity involving the cerebellum. The fundamental nature of the entity and its pathogenesis remain unknown, and considerable debate has centered on whether it represents a neoplastic, malformative or hamartomatous lesion. The cell or cells of origin remain incompletely defined. Previous reports of cases in the English literature have dealt predominantly with the clinical and pathological aspects yet few address issues of treatment.

A case of Lhermitte-Duclos disease (LDD) in a 54-year-old female leading to local compressive symptoms and obstructive hydrocephalus is presented. A craniectomy, in addition to a CI laminectomy followed by a decompressive duroplasty (using autologous fascia lata graft) was performed.

The patient clinically improved and follow-up MRI 11 months post-operatively revealed improvement in hydrocephalus.

The histological and immunohistochemical features of the lesion are described, emphasizing the role of an abnormal dysplastic granule cell layer. The evidence in favor of each of the major theories of pathogenesis, malformative and neoplastic is discussed. Based on these facts a form of surgical intervention involving decompressive duroplasty is proposed.

Complex auditory hallucinations have rarely been reported in cases of brainstem stroke or tumor.

Case study.

A patient with acute Listeria rhombencephalitis complained of formed musical auditory hallucinations on the side of recent sensorineural deafness. MRI revealed an abscess in the middle cerebellar peduncule with extensive surrounding edema.

Disruption of brainstem auditory pathways may cause complex auditory hallucinations. Potential pathogenetic mechanisms are discussed and a diagnostic approach is proposed.

A seizure is the most common cause of loss of driving privileges for medical reasons but there is variability in how physicians and the authorities who regulate driving approach this issue.

A questionnaire regarding epilepsy and driving was sent to all adult neurologists in Canada (n = 494).

Of 289 (59%) neurologists responding, 50% usually report patients with seizures to the department of motor vehicles compared to only 4% for stroke/TIA, 26% for dementia and 8% for other neurologic disorders (p < 0.0001). In the five provinces with mandatory reporting laws, seizures were reported most of the time by 84% compared to only 19% in the five provinces with discretionary reporting (p < 0.0001). Nationwide, 44% agreed with mandatory reporting but this also differed in provinces with and without mandatory reporting legislation (63% vs. 37%, p < 0.0001). Only 49% agreed with the current recommendation of at least one year seizure free interval before resuming driving.

Seizures are disproportionately reported compared to other neurological conditions. Many neurologists disagree with the recommended Canadian standards for duration of driving restriction after seizures. Variability in the attitude and practice of neurologists in regard to reporting of seizures is confirmed.