To review the demographics and workload characteristics of pediatric neurology in Canada.

A standardized survey questionnaire was mailed out to practicing pediatric neurologists in Canada in 2001. Variables examined were age, gender, hours on call, regular hours worked per week, type of practice and projected changes in practice over next five to ten years. Results were compared to the 1994 Pediatric Neurology Manpower Survey which had used the same survey instrument.

Fifty-six (70%) pediatric neurologists practicing in Canada returned the survey. As was the case in 1994, no significant differences in workload were found based on age or gender. The average age of the practicing pediatric neurologist in 2001 was 51 years compared to 45 years in 1994. The proportion of physicians over 55 years in 2001 was 35% compared to 25% in 1994.

Pediatric neurology in Canada is an aging specialty needing a significant recruitment of new members.

Prevention of bilirubin encephalopathy relies on the detection of newborns who are at risk of developing serious hyperbilirubinemia. The objective of this study was to reassess the clinical syndrome of kernicterus as neurodiagnostic studies have become more readily available and can be used to evaluate these infants.

The study population was neonates born at term or near term admitted to The Hospital for Sick Children in Toronto, Ontario, Canada, between January 1990 and May 2000. During the study period, there were 9776 admissions (average number of admissions per year – 888 infants). The inclusion criteria were that patients had total serum bilirubin levels of > 400μmol/L at the time of diagnosis and no evidence of hypoxic ischemic encephalopathy. Records were reviewed to establish neurodevelopment outcomes.

Twelve neonates (nine males) were identified. Bilirubin levels at the time of diagnosis ranged from 405 to 825μmol/L. Causes of these elevated levels included glucose-6-phosphate dehydrogenase deficiency (seven patients), dehydration (three patients), sepsis (one patient), and was undetermined in one patient. Abnormal visual evoked potentials were found in three of nine patients and abnormal brainstem auditory evoked potentials in seven of ten patients. Abnormal electroencephalograms were documented in five patients studied. Brain magnetic resonance imaging results were abnormal in three of four patients.

Magnetic resonance imaging typically showed an increased signal in the posteromedial aspect of the globus pallidus and was, therefore, useful in the assessment of the structural changes of chronic bilirubin encephalopathy after kernicterus.

Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive disorder which presents with recurrent myoglobinuria. Heterozygotes are usually asymptomatic.

We correlate the clinical, biochemical and molecular features of a family in which the proband is homozygous for CPT II deficiency, due to the common Ser 113 Leu mutation.

The 20-year-old female proband presented at age three years with episodic myalgia and myoglobinuria, elevated creatine kinase (CK) of 3600 IU/L and had a 33% residual CPT II activity in cultured skin fibroblasts. Her 25-year-old dizygotic twin brothers presented with muscle stiffness following prolonged exercise but no overt pigmenturia and had interictal CKs up to 662 IU/L. Her parents and a 13-year-old brother are asymptomatic. An elder sister, not investigated, had recurrent pigmenturia and died at eight years with myoglobinuria. Molecular analysis revealed that the proband is homozygous for the Ser 113 Leu mutation. Her parents are heterozygotes with CPT II activities of 55% to 70%. Her younger brother is normal with 83% activity. The symptomatic twin brothers are heterozygous but demonstrated unexpectedly low CPT II activities of 40%, which may explain their phenotype.

We postulate that there may be genetic, environmental and sex hormonal factors accounting for this manifesting heterozygosity and biochemical heterogeneity in CPT II deficiency.

Rett syndrome (RTT) is a severe neurodevelopmental disorder of girls, caused by mutations in the X-linked MECP2 gene. Worldwide recognition of the RTT clinical phenotype in the early 1980's allowed many cases to be diagnosed, and established RTT as one of the most common mental retardation syndromes in females. The years since then led to a refinement of the phenotype and the recent elaboration of Revised Diagnostic Criteria (RDC). Here, we study the impact of the presence versus the absence of the use of diagnostic criteria from the RDC to make a diagnosis of RTT on MECP2 mutation detection in Canadian patients diagnosed and suspected of having RTT.

Using dHPLC followed by sequencing in all exons of the MECP2 gene, we compared mutation detection in a historic cohort of 35 patients diagnosed with RTT without the use of specific diagnostic criteria to a separate more recent group of 101 patients included on the basis of strict fulfillment of the RDC.

The MECP2 mutation detection rate was much higher in subjects diagnosed using a strict adherence to the RDC (20% vs. 72%).

These results suggest that clinical diagnostic procedures significantly influence the rate of mutation detection in RTT, and more generally emphasize the importance of diagnostic tools in the assessment of neurobehavioral syndromes.

Doppler ultrasound (DUS) is used as a screening tool to assess internal carotid artery (ICA) disease. Recent reports suggest that the DUS may be inaccurate in over 28% of patients. We sought to evaluate the accuracy of DUS, when performed in a dedicated stroke prevention clinic (SPC).

We retrospectively reviewed the charts of patients who had a DUS performed in our SPC, followed by conventional cerebral angiography. Three groups of patients were defined. Group 1 had DUS measured ICA stenosis of >50%; Group II had a DUS measured ICA stenosis of <50%; Group III had complete ICA occlusion on DUS.

Sixty-seven patients (69 arteries) were included in the study. There were 45 patients in Group I and based on the findings of cerebral angiography, carotid endarterectomy was considered inappropriate in only one patient. - a misclassification rate of 2.2% (95%CI: 0 – 6.5%). Group II consisted of 19 patients and on cerebral angiography, none of these patients had a stenosis of >50% - a misclassification rate of 0%. Group III consisted of five patients in whom DUS showed complete ICA occlusion. The angiogram confirmed the occlusion in all five patients – a misclassification rate of 0%. Overall, misclassification rate was 1.45% (95% CI: 0 - 4.3%).

Doppler ultrasound when performed in a stroke prevention clinic (SPC), has a high accuracy in measuring ICA stenosis of >50%. Doppler ultrasound is reliable in detecting complete ICA occlusion and finally DUS is a reliable screening tool to rule out clinically significant ICA stenosis.

To determine physical and cognitive outcomes of full-term infants who suffered intracranial hemorrhage (ICH) at birth.

A retrospective hospital-based, follow-up study of infants treated in London, Ontario between 1985 and 1996. Follow-up was conducted by telephone interviews and clinic visits. Outcome was measured according to physical and cognitive scales. Perinatal risk factors and hemorrhage characteristics were correlated with final outcome.

For this study 66 infants with ICH were identified, of which seven died during the first week of life. We obtained follow-up in all but ten cases (median = 3-years; range 1.0 to 10.9 years). Overall, 57% of infants had no physical or cognitive deficits at follow-up. Death occurred most frequently among those with primarily subarachnoid hemorrhage (19%) and the most favorable outcomes occurred among those with subdural hemorrhage (80% had no disability). In univariate models, thrombocytopenia (platelet count ≤ 70 x 109/L), increasing overall hemorrhage severity, frontal location and spontaneous vaginal delivery as opposed to forceps-assisted delivery increased risk for poor outcome. In multivariate models, all these factors tended towards increased risk, but only thrombocytopenia remained significant for physical disability (OR = 7.6; 95% CI = 1.02 – 56.6); thrombocytopenia was borderline significant in similar models for cognitive disability (OR = 4.6; 95% CI = 0.9 – 23.9).

Although forceps-assisted delivery may contribute to ICH occurrence, our study found better outcomes among these infants than those who had ICH following a spontaneous vaginal delivery. Hemorrhage in the frontal lobe was the most disabling hemorrhage location and if multiple compartments were involved, disability was also more likely to occur. However, in this report we found that the factor that was most likely to contribute to poor outcome was thrombocytopenia and this remained important in multivariate analysis.

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

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

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

Methadone appears to have unique properties including N-methyl-D-aspartate antagonist activity that may make it especially useful in the management of intractable neuropathic pain. This observation needs to be tested in randomized, controlled trials.

Controversial data was published about the sodium channel-blocking effect of the endogenous pentapeptide QYNAD, which is elevated in patients with multiple sclerosis and Guillain-Barré-syndrome. In some experiments with single cells and nerve preparations QYNAD inhibited sodium currents to the same extent as the known sodium channel blocker lidocaine whereas in other laboratory testing QYNAD failed to show any effect at all.

Micro-electrode arrays with cultured neuronal networks are highly suitable to determine neuroactive activity of applied substances. The impact on electrophysiological parameter changes was compared between QYNAD and the established sodium channel blockers lidocaine and tetrodotoxin (TTX).

QYNAD did not alter network activity whereas the sodium channel blockers lidocaine (IC50 14.9 µM) and tetrodotoxin (IC50 1.1 nM) reversibly decreased network activity in similar concentrations as in patch-clamp experiments. This decrease of spontaneous electrophysiological activity was achieved by prolonging the interburst-interval.

Although QYNAD might have mild effects on single-cell sodium currents, there is no significant effect on neuronal network function. These results raise concerns about QYNAD exhibiting a relevant impact on functional disability of the central nervous system in patients.

Transient focal lesions in the splenium of the corpus callosum (SCC) have been previously described in patients with epilepsy or without epilepsy but receiving antiepileptic drugs (AED).

Two epileptic patients were admitted to our long-term monitoring unit. Antiepileptic drugs were completely discontinued a few days later. One patient had no seizures. The other had three attacks, the last of which occurred two days before a brain magnetic resonance imaging (MRI) was performed. In both cases brain MRI showed a lesion in the SCC characterized by high signal on T2-weighted images and no enhancement after Gadolinium infusion. The patients were discharged with their pre-admission medications. A follow-up MRI five weeks later showed resolution of the SCC lesions.

The pathogenesis of transient SCC lesions in epileptic patients is still unclear. In our patients, either the sudden AED withdrawal or the seizures activity may be presumed to be the cause, though an individual susceptibility must also be considered.

Acute neurological deterioration secondary to cervical disc herniation not related to external trauma is very rare, with only six published reports to date. In most cases, acute symptoms were due to progression of disc herniation in the presence of pre-existing spinal canal stenosis.

A 42-year-old man developed weakness and numbness in his arms and legs immediately following a sneeze. On physical examination he had upper motor neuron signs that progressed over a few hours to a complete C5 quadriplegia. An emergent magnetic resonance imaging study revealed a massive C4/5 disc herniation. He underwent emergency anterior cervical discectomy and fusion. Postoperatively, the patient remained quadriplegic. Eighteen days later, while receiving rehabilitation therapy, he expired secondary to a pulmonary embolus. Autopsy confirmed complete surgical decompression of the spinal cord.

Our case demonstrates that acute quadriplegia secondary to cervical disc herniation may occur without a history of myelopathy or spinal canal stenosis after an event as benign as a sneeze.

Many anomalies and variants in vascular anatomy have been reported in relation to the anterior cerebral artery (ACA). Patients and

We encountered an apparently novel anomaly in a 30-year-old man admitted for disturbance of consciousness following a traffic accident. Computed tomography revealed an acute subdural hematoma and subarachnoid hemorrhage.

No vascular abnormalities related to the hemorrhage were detected by conventional angiography, so we concluded that the bleeding was of traumatic origin. Anomalous origin of the ACA was disclosed incidentally, with both A1 segments arising from the right internal carotid artery; no normal A1 segment of the left ACA was visualized. We discuss possible bases for this anomalous origin.

Spontaneous spinal epidural hematoma is a rare phenomenon that has no distinct etiology. Spontaneous spinal epidural hematoma (SSEH) during pregnancy is extremely rare. We present what we believe to be the fifth reported case of spontaneous spinal epidural hematoma associated with pregnancy in the English literature.

A 31-year-old female presented with acute onset of paraplegia at 32 weeks of pregnancy. The patient had a T2 sensory level and complete paralysis of all lower extremity motor groups. Magnetic resonance imaging of the thoracic spine showed an acute epidural hematoma posterior to the thoracic spinal cord between the second and fourth thoracic vertebrae.

The patient was taken to the operating room were her child was delivered by caesarean section. She then underwent a posterior laminectomy and evacuation of a spinal epidural hematoma. Followup selective spinal angiography was negative for any vascular malformation. The patient gradually recovered lower extremity function and was independently ambulating at six month follow-up. Voluntary bowel and bladder function returned within four months but twice daily intermittent catheterization remained necessary for excessive post-void residual urine.

Spontaneous spinal epidural hematoma in pregnancy is a rare phenomenon. It is postulated that elevated venous pressure associated with pregnancy may be a contributing factor. In the reported cases of SSEH in pregnancy most patients presented with acute symptoms, thoracic location and profound neurological deficits but, with prompt surgical treatment, generally had good long term recovery.

Interferon β has become standard therapy for reducing relapse frequency in relapsing/remitting Multiple Sclerosis (RRMS). Several different preparations are available including interferon β1a (Avonex, Rebif) and interferon β1b (Betaferon/Betaseron). For the most part these preparations have been considered safe. Recently there have been concerns relating to liver1 and now kidney toxicity.

We present a case of a 28-yr old male who developed a severe case of nephrotic syndrome while being treated for relapsing/remitting Multiple Sclerosis (RRMS) with weekly injections of interferon β1a.

The nephrosis resolved almost completely once the interferon was stopped and after immunosuppressive treatment. At its peak the daily protein loss was 35.82 g. Kidney biopsy demonstrated membranous glomerulonephritis.

Two other case reports of nephrotic syndrome have been reported in the literature. This latest (third) report suggests that the safety profile should be reexamined and at least raises the question of potential renal toxicity of interferons in MS.