The safety, tolerability, efficacy, and impact on quality of life of gabapentin (Neurontin®) as adjunctive therapy to carbamazepine (CBZ) and/or phenytoin (PHT) was assessed in epileptic patients with partial seizures.

NEON (Neurontin Evaluation of Outcomes in Neurological Practice) was an open-label, prospective, multicentre study conducted in patients on a stable dose of CBZ and/or PHT and experiencing an average of up to 4 complex partial seizures with or without secondary generalization per month, with no seizure-free months. The treatment lasted 20 weeks. Gabapentin was started at 400 mg/day and was individually titrated to effective tolerable dose up to 2400 mg/day. Quality of life was evaluated using the QOLIE-10 questionnaire.

A total of 141 patients were enrolled at 36 sites; 114 patients were evaluable for efficacy analyses. The mean maintenance dose of gabapentin was 1600 mg/day (range = 300-3200). A decrease of 50% or more in frequency of complex partial + secondarily generalized seizures was observed in 81 (71 %) patients (p = 0.0001). Fifty two (46%) patients were seizure-free during the last 8 weeks of treatment. A significant improvement (p < 0.05) was observed in 5 of the 10 questions of the QOLIE-10, as well as in the composite QOL score (p = 0.0002). The most frequent adverse events included somnolence (16%), dizziness (9%), and asthenia (6%). Twenty-five (18%) patients prematurely discontinued the study, 16 (11%) of them due to adverse events.

This study indicates that treatment with gabapentin as adjunctive therapy to standard antiepileptic drugs in this group of patients not only provides significant improvement in seizure control, but also has a positive impact on quality of life. The clinical benefits in efficacy, safety and tolerability demonstrated at 20 weeks are sustained, and no tolerance develops with gabapentin in longer term use.

Machado-Joseph disease (MJD) is a dominantly inherited cerebellar ataxia associated with spasticity, ophthalmoplegia and dystonia. There has been no report of electrophysiological or histological alterations of the peripheral nervous system in patients with MJD.

Four patients with MJD were identified by polymerase chain reaction. The peripheral nerves of these patients were subjected to electrophysiological testing and histological study. Correlation analyses were made between various clinical parameters and the electrophysiological and histological changes.

Electrophysiological studies demonstrated a marked reduction of sensory action potential, acute denervation changes on needle EMG, as well as mild decrease in the compound motor action potential. Light microscopy of the sural nerves revealed clear loss of myelinated fibers, and morphometry studies showed a loss of large myelinated fibers. Moreover, the severity of these pathological changes was found to be related to the CAG repeat length in the MJD gene.

Our findings indicated that the peripheral nervous system was frequently affected in patients with MJD. These findings were similar to those seen in Friedreich's ataxia, suggesting a loss of sensory and motor fibers probably following a lesion of the dorsal root ganglion and the anterior horns in the spinal cord. Furthermore, the number of CAG repeats seems to have an inverse relationship to the extent of pathological changes of the peripheral nerves.

To study the clinical features and treatment given to episodic cluster headache patients in the Calgary region.

Fifty-one (51) patients who responded to a media campaign, had previously been diagnosed by their family physicians, and who met International Headache Society (IHS) criteria for episodic cluster headache, formed the population for this study.

The media campaign consisted of newspaper advertisements and radio publicity including physician interviews and talk shows. Patients were required to complete a 200-item questionnaire detailing clinical features and treatment of their cluster headache syndrome. Each patient was also interviewed by our research nurse for clarification and proper completion of questionnaire.

Fifty-one percent (51%) of our patients had short headache attacks lasting one hour or less. Almost one-half (45%) had three or four attacks per 24 hour period. Eighty-six percent (86%) had been referred to a neurologist. Sixty-nine percent (69%) had never used oxygen, but of those who had, onehalf were still using it. Sumatriptan by injection had been tried by 26% of patients and of these, 93% considered it effective. Subcutaneous dihydroergotamine had been tried by 8%. For prophylaxis, 41% had tried methysergide, 31% prednisone, and 4% verapamil. Many patients had been prescribed migraine prophylactic drugs which are ineffective for cluster headache, and some had also undergone dental procedures or nasal and sinus surgeries.

Many cluster headache patients had not, to their knowledge, been prescribed or used the best symptomatic and prophylactic treatments for cluster headache. This should be addressed through educational programs and through making up-to-date information on the treatment of cluster headache readily available to physicians and patients.

Despite the common association of psychiatric morbidity and multiple sclerosis (MS), population-based prevalence estimates of these disorders are limited. Such estimates are of particular importance to those conducting trials of interventions for the treatment of MS. This study examined the prevalence of bipolar disorder, depression, and attempted suicide among hospital service utilizers in Nova Scotia and compared these measures for the MS and non-MS population.

Data regarding diagnosis and utilization were extracted from two linked databases which included all hospital separation records for Nova Scotia over a 3 year period (1992/93-1994/95).

The prevalence of bipolar disorder in hospitalized MS patients was 1.97% and depression was 4.27%. These rates were significantly higher than the 0.92% and 2.04%, respectively, for the non-MS hospital utilizers. These diagnoses also accounted for more than half of the primary diagnostic codes for psychiatric service separations by MS patients. The proportion of total hospital utilization which was accounted for by psychiatric services did not differ between MS and non-MS utilizers. While suicide attempts were rare, the estimated frequency of suicide attempts in the total MS population was more than three times that of the general population.

Bipolar disorder and depression were twice as prevalent in hospitalized MS patients as in the general population of hospital utilizers while the estimated frequency of suicide attempts was at least three times greater. These results illustrate that psychiatric morbidity and service utilization are important considerations in the care of MS patients.

Segmental hyperhidrosis is an uncommon finding which is usually associated with irritation or infiltration of pre-ganglionic sympathetic fibres or the sympathetic chain.

We report two cases of segmental hyperhidrosis with striking clinical features.

In one case, a mesothelioma produced ipsilateral simultaneous underactivity and overactivity of sympathetic outflow and in the other case a thoracic central disc herniation was probably responsible for a band of sweating which clearly extended beyond the segmental level of injury.

Segmental hyperhidrosis should trigger a search for structural disease in the spinal and paraspinal region.

Antibodies to cardiolipin and other phospholipids have been associated with recurrent thrombotic events, including stroke.

Over a 16 month period we assessed an unselected cohort of 151 ischemic stroke patients for the presence of antiphospholipid antibodies. Patients with known systemic lupus erythematosis, systemic sclerosis, or Sjogrens Syndrome were excluded. Sera from patients admitted to hospital with a diagnosis of ischemic stroke (n = 151) and from controls (n = 111) assessed during the same period were tested for antiphospholipid antibodies (APLA) using 3 assays; anticardiolipin antibodies (ACA) by ELISA, prolonged activated partial thromboplastin time (APTT), and VDRL.

The average age of ischemic stroke cases was 68 years (range 29 to 91) and of controls 63 years (range 29 to 86). The prevalence of APLA detected by at least one of the three methods was 12% for IS cases and 10% for controls. After correcting for known risk factors such as age, gender, diabetes mellitus, heart disease, hypertension, and smoking, the odds ratio for risk of stroke fell to 0.8 (C.I. 0.4 to 1.2).

Our findings suggest that APLA may not be an independent risk factor for ischemic stroke in unselected persons who do not have known systemic lupus erythematosis or systemic sclerosis but further evaluation of the role of lupus anticoagulant is indicated.

Since few studies have examined the effectiveness of therapies for subcortical vascular dementia, treatment guidelines are not available. Current patterns in the treatment of such dementias have not been studied.

To determine the practice patterns of Canadian specialists for the treatment of subcortical vascular dementia, and to survey their opinions regarding issues which are important in the design of a randomized controlled trial (RCT) in this field.

National survey of all specialists certified in Neurology or Geriatric Medicine.

Of responding physicians (78%) prescribed antithrombotic therapy for patients with vascular dementia. Most begin treatment with aspirin 325 mg daily (64%). The next three most common initial treatments were; no pharmacotherapy (12%), aspirin 650 mg daily (11%), and aspirin 1300 mg daily (11%). If the dementia continued to progress despite initial therapy, the treatment options were more varied. Most specialists (69%) believed that an RCT to assess the efficacy of aspirin in vascular dementia is warranted. The majority (69%) also felt that serial neuroimaging would be required for participants in such a trial, with magnetic resonance imaging being cited most frequently (41%). The majority of specialists considered three years as the minimum durationb for such a trial.

Specialist physician practice patterns vary significantly for the treatment of patients with subcortical vascular dementia. Most physicians believe that an RCT testing the efficacy of aspirin in this condition is required. However, before such a trial can be conducted, many methodological difficulties need to be addressed.

The treatment of chronic daily headache (CDH) due to medication overuse remains a common and difficult problem. For selected patients refractory to outpatient management we have used a treatment protocol using dihydroergotamine (DHE) as introduced by Raskin, during a brief (typically 48 hours) in-patient stay. While many studies have documented the short-term efficacy of the DHE protocol, there are limited data on its long-term effects. The purpose of this study was to evaluate the efficacy of the protocol on headache frequency and severity, analgesic use, absences from work, and quality of life, at three months post treatment and the present time.

A retrospective chart review of all patients admitted for the DHE protocol from 1991 to 1996 revealed 174 cases. Of these, 132 patients were interviewed by phone.

The DHE protocol was shown to decrease headache frequency, severity, headache medication use, and absences from work both at three months and the time of interview.

This study has the largest patient base and the longest follow-up period for the use of DHE for CDH. The results confirm that the DHE protocol is helpful in breaking the cycle of CDH, although the long-term outcomes of this study are more conservative than other studies have reported.

We report a possible risk factor which could identify patients with chronic hydrocephalus who are at risk for sudden death.

A retrospective review of medical records and computed tomographic (CT) scans was conducted on three patients with chronic hydrocephalus who suffered acute cardiorespiratory arrest without those signs which are normally associated with a progressive worsening of hydrocephalus.

All three of these patients were awake and communicative shortly before the life threatening or terminal event. All had experienced some recent worsening of neurologic signs or symptoms, but none had shown a progressive impairment of consciousness or major neurologic decline ordinarily associated with life threatening elevation of intracranial pressure. Absence of the perimesencephalic cisterns on head CT scans done prior to or just after the life threatening event was the only new radiologic finding common to all these patients.

The absence of the perimesencephalic cisterns in an awake and alert patient with severe hydrocephalus indicates that the patient may be at risk for neurogenic cardiorespiratory failure. In such cases, (especially when there has been a recent, albeit mild, change in neurologic signs or symptoms), the neurologist should urge emergency ventriculostomy or shunting for the hydrocephalus.

The present study was designed to find the differences in regional cerebral blood flow and cerebrovascular acetazolamide reactivity between leuko-araiosis with and without lacunar infarction.

Fifteen cases of leuko-araiosis with lacunar infarction, 15 cases of leuko-araiosis without lacunar infarction and 15 age-matched controls in which leuko-araiosis and cerebrovascular diseases are absent (control group) were studied. The regional cerebral blood flow was measured using the stable xenon computed tomography method before and 20 minutes after intravenous injection of 17 mg/kg acetazolamide.

The blood flows in the leuko-araiosis area and the lacunar area were significantly lower than the blood flow in the cerebral white matter. The blood flows in the cerebral cortex and the cerebral white matter were significantly lower in the leuko-araiosis with lacunar infarction group than in the leuko-araiosis without lacunar infarction group and the control group. The cerebrovascular acetazolamide reactivity in the leuko-araiosis area and the lacunar area was significantly lower than that in the cerebral white matter. The cerebrovascular acetazolamide reactivity in the cerebral cortex and the cerebral white matter was significantly lower in the leuko-araiosis with lacunar infarction group than in the leuko-araiosis without lacunar infarction group and the control group.

The degree of arteriolosclerosis is considered to be more severe and the rate of association of hypertension was higher in leuko-araiosis with lacunar infarction than in leuko-araiosis without lacunar infarction.

Myasthenia gravis (MG) is a specific autoimmune disease characterized by weakness and fatigue. MG may affect also the respiratory muscles causing symptoms that may vary from dyspnea on severe exertion to dyspnea at rest. This study was undertaken in order to determine the effects of respiratory muscle training on respiratory muscle performance, spirometry data and the grade of dyspnea in patients with moderate to severe generalized MG.

Eighteen patients with MG were studied and divided into 2 groups: Group A included 10 patients (3 males and 7 females aged 29-68) with moderate MG, and Group B that included 8 patients (5 males and 3 females aged 21-74) with severe MG. Patients in Group A received both inspiratory and expiratory muscle training for 1/2 h/day, 6 times a week, for 3 months, while patients in Group B followed the same protocol but had inspiratory muscle training only.

Mean PImax increased significantly from 56.6 ± 3.9 to 87.0 ± 5.8 cm H20 (p < 0.001) in Group A, and from 28.9 ± 5.9 to 45.5 ± 6.7 cm H20 (p < 0.005) in Group B. The mean PEmax also increased significantly in patients in Group A, but remained unchanged in the patients in Group B. The respiratory muscle endurance also increased significantly, from 47.9 ± 4.0 to 72.0 ± 4.2%, p < 0.001, in patients of Group A, and from 26.0 ± 2.9 to 43.4 ± 3.8, p < 0.001, in patients in Group B. The improved respiratory muscle performance was associated with a significant increase in the FEV, values, and in the FVC values, in patients of both groups. Mean dyspnea index score also increased significantly from 2.6 ± 0.8 to 3.6 ± 0.4 (p < 0.005) in Group A, and from 0.7 ± 0.2 to 2.0 ± 0.2 (p < 0.001) in Group B.

Specific inspiratory threshold loading training alone, or combined with specific expiratory training, markedly improved respiratory muscle strength and endurance in patients with MG. This improvement in respiratory muscle performance was associated with improved lung function and decreased dyspnea. Respiratory muscle training may prove useful as a complementary therapy with the aim of reducing dyspnea symptoms, delay the breathing crisis and the need for mechanical ventilation in patients with MG.

Cerebrovascular complications of meningitis have been most extensively documented in the setting of acute bacterial or chronic tuberculous meningitis. Involvement of major cerebral vessels is rare and basilar artery thrombosis has not been reported in fungal meningitis secondary to Candida infection.

We describe the clinical course and neuropathological findings in a woman with chronic meningitis due to Candida albicans.

The diagnosis remained elusive antemortem despite analysis of 7 large volume CSF samples and examination of a meningeal and cortical biopsy. Death followed extensive brainstem and temporo-occipital infarction secondary to basilar artery thrombosis. The basilar artery occlusion was secondary to an intense, granulomatous and necrotizing basal meningitis focally extending to the media and intima.

This paroxysmal and devastating complication of untreated chronic candida meningitis reinforces that a trial of empirical therapy with both antituberculous and antifungal agents should be considered in most cases of chronic culture-negative lymphocytic meningitis.

Previous studies demonstrated controversial results regarding monoamine oxidase B (MAO-B) activity in platelets in the periphery in parkinsonian patients (PD).

Therefore we determined platelet MAO-B activity in three age- and sex-matched groups of 17 untreated, so called “de novo” patients with Parkinson's disease (PD), 17 parkinsonian patients, receiving levodopa, and 17 controls by a radio enzymatic assay.

No significant differences of MAO-B activity appeared.

This result suggests that phenotypic determination of MAO-B activity in platelets may not be used as peripheral marker in PD and that levodopa treatment does not alter MAO-B activity in the periphery.