We report a multigenerational family with uncomplicated hereditary spastic paraplegia type 4 and apparent anticipation. Genetic analysis of the proband revealed a frame shift mutation (5 base pair deletion) in exon 9 of the SPG4 gene encoding the spastin protein. We hypothesized that this deletion mutation may be dynamic and variability in the size of the deletion could account for the anticipation.

Clinical and genetic analysis of this family and the deletion mutation.

In this family, the age of onset, which ranges from 3 to 50 years shows an average decrease in the age of onset of 21.8 years per transmission over three generations. Genetic analysis of multiple family members indicates that all affected members carry the same c.1340_1344deITATAA mutation and that it is not dynamic.

In this family, other molecular mechanisms may contribute to development of anticipation.

Very long term survival after diagnosis of malignant glioma has been described in individual case reports. Survival of more than 10 years is extremely rare, especially when identified in 3 out of 71 patients assigned to one arm of a randomized controlled trial.

Three patients survived 11, 16, and 18 years following the diagnosis of glioblastoma and treatment with surgery, conventional fractionated radiation, and high-activity iodine-125 boost brachytherapy as part of a randomized controlled trial.

Despite this apparent cause and effect relationship, statistical analysis shows no relationship between these cures and treatment with brachytherapy. Cure of glioblastoma remains rare.

The most common cause of autosomal dominant Hereditary Spastic Paraplegia (HSP) is mutations in the SPG4 gene. We have previously identified novel SPG4 mutations in a collection of North American families including the c.G1801A mutation present in two families from Quebec. The aim of this study is to estimate the frequency of the c.G1801A mutation in the French Canadian (FC) population and to determine whether this mutation originates from a common ancestor.

We collected and sequenced exon 15 in probands of 37 families. Genotypes of markers flanking the SPG4 gene were used to construct haplotypes in five families. Clinical information was reviewed by a neurologist with expertise in HSP.

We have identified three additional unrelated families with the c.G1801A mutation and haplotype analysis revealed that all five families share a common ancestor. The mutation is present in 7% of all our FC families and explains half of our spastin linked FC families. The phenotype associated with the c.G1801A genotype is pure HSP with bladder involvement.

In this study we have determined that the relative frequency of the c.G1801A mutation in our FC collection is 7%, and approximately 50% in the spastin positive FC group. This mutation is the most common HSP mutation identified in this population to date and is suggestive of a founder effect in Quebec.

Our objective is to examine how persons diagnosed with Multiple Sclerosis (MS) and Parkinson's disease (PD) change residence following disease onset. We hypothesize that persons choose to change residence (locally or regionally) in different ways depending on whether or not they have been diagnosed with MS/PD. We also estimate the effects of residence change on measures of disease prevalence made at several different levels of geography.

Using fee-for service and hospitalization data, we identify cases of MS and PD between 1994 and 2004. Both of these case groups are matched to controls based on age, sex, socioeconomic status and municipality of residence. We tabulate and compare the changes of residence among persons in the case and control groups. We also use these data to estimate the effects that changes in residence have on disease prevalence at three different levels of geography.

Both MS and PD patients were more likely to change residence following disease onset compared to groups of matched controls (p<=0.001). Most changes of residence occur within the same municipality. The total magnitude of these changes is small, however, and is unlikely to affect estimates of disease prevalence; over our study period, the largest change in geographical prevalence estimates due to individual changes in residence was about 1%.

Persons diagnosed with MS and PD both have mobility characteristics that differ from those of their respective control groups, and in general, are more likely to move to or between Edmonton and Calgary, and less likely to move out of province. However, the balance of mobility characteristics of persons with PD and MS appear unlikely to greatly affect the patterns observed on maps of disease prevalence.

To determine the demographic and clinical data of Thai multiple sclerosis (MS) patients.

A retrospective study of 72 patients attending the MS clinic at Siriraj Hospital, Mahidol University, Thailand between January 1997 and June 2004.

Fifty-eight patients (81%) were classified as clinically definite MS, 5 (7%) as Devic's syndrome, and 9 (13%) as possible MS. There were 62 females (86%) and 10 males (14%). Age at onset was 33 ± 12 years with a mean relapse rate of 1.2 ± 1.0 attacks per annum. None had a family history of MS. Visual impairment (53%) was the most common manifestation. Only 16% had classic (western) form of MS. Positive oligoclonal bands were found in 21%, visual evoked potentials with a typical delayed latency in 28%. MRI brain lesions compatible with McDonald's criteria were seen in only 24%, and spinal MRI brain longer than 2 vertebral bodies in 62%. The mean Kurtzke's Expanded Disability Status Scale (EDSS) was 3.0.

Thai MS patients had much more female occurrence, no family history, common optico-spinal form, long spinal MRI lesions and low positive CSF oligoclonal bands.

Neuropathological changes in degenerating motor neurons are well documented in the term neonate with spinal muscular atrophy, but not at midgestation.

Postmortem neuropathological examination was performed in a 20-week male fetus with a hypoplastic left cardiac anomaly.

Selective degeneration of spinal and hypoglossal motor neurons was an incidental finding. Degenerating motor neurons were not immunoreactive with neuronal nuclear antigen (NeuN) or neuron-specific enolase (NSE), as were the normal motor neurons. Synaptophysin reactivity was reduced around the soma of degenerating normal motor neurons. Ubiquitin and tau were expressed in degenerating motor neurons. Gliosis, inflammation and microglial activation were lacking in the ventral horns of the spinal cord. Laryngeal striated muscle was unaltered for age. No cerebral malformations or hypoxic-ischaemic changes were found.

This case represents an early motor neuronal degeneration and corresponds to the recently described “type 0” spinal muscular atrophy. Lack of contractures is attributed to the early fetal age, since most muscular growth occurs in the second half of gestation.

This critical review provides a summary of the clinical presentation, neuroimaging, treatment and prognosis in pediatric ophthalmoplegic migraine (OM). The features of OM are not in keeping with its classification as a migraine-variant.

We review 3 new and 37 reported pediatric OM cases.

Headache was an inconsistent feature, with 25% patients showing no evidence of pain at the initial OM episode.

1) prolonged time for symptom resolution to occur (median time 3 weeks); 2) tendency for recurrent episodes to have more severe and persistent nerve involvement; 3) evidence of permanent neurological sequelae with recurrent episodes (30% of patients); 4) rapid improvement and shortened duration with corticosteroid therapy and; 5) transient, reversible MRI contrast enhancement of the affected cranial nerve (86% of patients). These features would not be expected in primary migraine headache.

A detailed understanding of the natural history of OM is essential for the clinical. This review provides support that OM may result from cranial nerve inflammation with headache a secondary and later feature of this condition.

Oxidative stress largely contributes to early brain injury after subarachnoid hemorrhage (SAH). One of the major sources of reactive oxygen species is NADPH oxidase, upregulated after SAH. We hypothesized that NADPH oxidase-induced oxidative stress plays a major causative role in early brain injury after SAH.

Using gp91phox knockout (ko) and wild-type (wt) mice, we studied early brain injury in the endovascular perforation model of SAH. Mortality rate, cerebral edema, oxidative stress, and superoxide production were measured at 24 h after SAH. Neurological evaluation was done at 23 h after SAH surgery.

Genotyping confirmed the existence of a nonfunctional gp91phox gene in the ko mice. CBF measurements did not show differences in SAH-induced acute ischemia between ko and wt mice. SAH caused a significant increase of water content in the ipsilateral hemisphere as well as an increase of Malondialdehyde (MDA) levels and superoxide production. There were no significant differences in post-SAH mortality rate, brain water content and the intensity of the oxidative stress between knockout and wild type groups of mice.

Our results suggest that gp91phox is not critically important to the early brain injury after SAH. An adaptive compensatory mechanism for free radical production in knockout mice is discussed.

Neurocardiogenic syncope (NCS) can be mistaken as a seizure. We reviewed the frequency and diagnostic consequences of this misdiagnosis.

A retrospective review of outpatient adult epilepsy clinic charts (QEII health Sciences Centre, Halifax, NS) was conducted to identify NCS patients referred with a provisional diagnosis of seizures. Charts were reviewed in detail with an emphasis on the consequences of misdiagnosis.

Of 1506 consecutive referrals to the epilepsy clinic, 194 (12.9%) ultimately had a clinical diagnosis of NCS. Mean age was 38 +/- 16 years (mean age of syncopal onset was 28 +/- 16 years). Two-thirds of referrals were from primary care physicians (including emergency departments) and 18% from neurologists. Thirty-five percent were prescribed antiepileptic drugs (AEDs) prior to referral with eight patients (4.1%) experiencing hypersensitivity reactions. Three of five women had adverse pregnancy outcomes while taking AEDs. One-third of patients had restrictions placed on their driving privileges while 11 patients (5.7%) had their employment interrupted. Diagnostic modalities used in the work-up included EEG (90%), CT head (51%), and MRI head (15%).

NCS is commonly misdiagnosed as epilepsy. Some patients had an incorrect diagnosis for > 10 years. Patients with this misdiagnosis are often excessively investigated, inappropriately treated, and have unnecessary restrictions placed on driving and employment.