The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques

To examine the longitudinal media reported rate of concussions in the National Hockey League (NHL) over the period 1986-87 to 2001-02. All injury reports published in the weekly sports newspaper The Hockey News for the 16 seasons 1986-87 through 2001-02 were reviewed for reported concussions. The Hockey News reports are based on weekly injury reports released by the NHL, which derive from reports submitted to the league by individual team offices. Adjusted for changes in the number of teams and games per season over the 16 year study period, and expressed as: number of concussions per 1000 games, results by season (starting with 1986-87) were 4, 8, 7, 7, 5, 5, 7, 7, 6, 8, 13, 20, 30, 27, 30, 25. Comparing each season with the prior season, significant increases were reported in 1997-98 and 1998-99 (p < 0.05 and 0.025, respectively), with no change since 1998-99. The reported concussion rate in the NHL during the last five years is more than triple that of the previous decade. Bigger, faster players, new equipment and harder boards and glass have all theoretically increased the risk of concussion in the NHL in recent years. However, the abrupt increase and subsequent plateau in concussion rate since 1997 suggests that increased recognition and reporting may be primarily responsible for the apparent increase in incidence.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) selectively destroys dopaminergic neurons in the pars compacta of the substantia nigra (A8 and A9 cells). MPTP or its metabolite enters nerve cells at the level of their terminals in the caudate nucleus and putamen leading to a disturbance in axoplasmic flow and retrograde degeneration. The species-dependent neurotoxicity of MPTP (primate vs. rodent) suggests that a biochemical property of the cell related to neuromelanin may be important in the mechanism of cell injury.

Our experience in treating 7 patients with moderate to severe parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is reviewed. Virtually all of the problems typically encountered with dopamine precursor and agonist therapy in treating Parkinson's disease have been observed during a one and one half year follow-up period, including "end-of-dose" deterioration (or "wearing off"), "peak-dose" dyskinesias, "on-off" phenomena, and psychiatric complications. These have occurred much earlier than is typically seen when treating the idiopathic disease. This rapid evolution of therapeutic side-effects favors the view that at least some of the complications of dopamine precursor therapy may be related to severity of disease rather than the length of levodopa therapy. Finally, we suggest that the occurrence of this full array of therapeutic complications in patients with MPTP-induced parkinsonism furthers the analogy between this syndrome ane Parkinson's disease.

This study demonstrates the utility of a newly-developed moveable 1.5 Tesla intraoperative MR imaging system using a case report of a multi-lobulated parafalx meningioma. A 43-year-old female presented with progression of a multi-lobulated anterior parafalx meningioma several years following resection of a large left frontal convexity meningioma. Surgical excision of the lesion was undertaken. Following apparent total resection, intraoperative MR imaging revealed two residual dumbell shaped lobules. Using these updated MR images, the tumour was readily identified and removed. The moveable 1.5 Tesla intraoperative MR system used in the present case provides rapid, high resolution MR images during neurosurgical procedures. Moving the magnet out of the surgical field during surgery permits the use of all standard neurosurgical instruments. The ease of use and quality of images combined with minimal interference on well-established surgical techniques makes this system a valuable adjunct in the neurosurgical treatment of intracranial disease.

In this study, we investigated the feasibility of using a 1.5 Tesla (T) clinical magnetic resonance imaging (MRI) system for in vivo assessment of three histopathologically different brain tumor models in mice. We selected mouse models in which tumor growth was observed in different intracranial compartments: Patched+/- heterozygous knock-out mice for tumor growth in the cerebellum (n = 5); U87 MG human astrocytoma cells xenografted to the frontal lobe of athymic mice (n = 15); and F5 (n = 15) or IOMM Lee (n = 15) human malignant meningioma cells xenotransplanted to the athymic mouse skull base or convexity. Mice were imaged using a small receiver surface coil and a clinical 1.5 T MRI system. T1- and fast spin echo T2-weighted image sequences were obtained in all animals. Gadolinium was injected via tail vein to better delineate the intracranial tumors. Twenty mice were followed by serial MRI to study tumor growth over time. In these mice, images were typically performed after tumor implantation, and at two week intervals. Mice were euthanized following their last imaging procedure, and their tumors were examined by histopathology. The histopathological preparations were then compared to the last MR images to correlate the imaging features with the pathology. Magnetic resonance imaging delineated th tumors in the cerebellum, frontal lobes and skull base in all mouse models. The detection of intracranial tumors was enhanced with prio administration of gadolinium, and the limit of resolution of brain tumors in the mice was 1-2 mm3. Sequential images performed at different time intervals showed progressive tumor growth in all animals. The MR images of tumor size and location correlated accurately with th results of the histopathological analysis. Magnetic resonance imaging of murine brain tumors in different intracrania compartments is feasible with a 1.5 T clinical MR system and a specially designed surface coil. Tumors as small as 1-2 mm3 can be detecte with good image resolution. Mice harbouring nascent brain tumors can be followed sequentially by serial MR imaging. This may allow for a noninvasive means by which tumor growth can be measured, and novel therapies tested without resorting to sacrifice of the mice.

As has been shown previously, S-100beta levels in serum can be a useful predictor of brain damage after head trauma. This pilot study was designed to investigate whether urine samples, which are much easier to obtain, could be used for the same purpose instead of serum samples. Ninety-six consecutive patients admitted with head trauma were recruited in the study. After exclusion of 54 patients, mostly because of significant additional trauma, S-100beta levels were analyzed in serum and urine of 42 patients using a luminometric assay. A range for normal values was established based on samples from ten healthy volunteers. S-100beta serum levels increased proportional to the severity of the head trauma, as had been previously shown by several other groups. In many patients, initial increases in urine S-100beta levels were seen later than in serum, after which the kinetics of S-100beta levels in urine seemed to follow that established for serum levels. S-100beta values in urine were on average about 54% lower in urine than in serum. S-100beta levels in urine obtained on admission to the hospital are not a good indicator for the extent of brain damage. However, urine S-100beta levels obtained at later time points might be a useful indicator for the development of secondary brain injury.

It has been shown previously that S-100beta levels in serum correspond with the severity of central nervous system (CNS) trauma. It also has been suggested that S-100beta in CNS tissue is involved in neuroprotection and neuroregeneration. We have previously shown that administration of quercetin results in improved motor function in an animal model of spinal cord trauma. Mid-thoracic spinal cord compression injury was produced in adult male Wistar rats. Serum and tissue samples were acquired from quercetin-treated animals (25 micromol/kg) and saline controls at 6, 12 and 24 hours after the trauma. S-100beta levels were measured using a luminometric assay in the damaged tissue and in the serum of the animals. The increase in serum S-100beta levels seen in saline controls after spinal cord trauma was ameliorated in the quercetin-treated animals at all time points, although the difference to saline controls became statistically significant only at 24 hrs after the trauma. Compared to tissue S-100beta levels in healthy animals, values were significantly decreased in saline controls at all three time points, while they were decreased at 6 hrs and increased at both 12 and 24 hrs in quercetin-treated animals. At all three time points tissue S-100beta levels were significantly higher in quercetin-treated animals than in saline controls. Administration of quercetin results in modification of S-100beta levels in the setting of experimental spinal cord trauma. The kinetic patterns of the S-100beta fluctuations in serum and tissue suggest that post-traumatic administration of quercetin decreases the extent of CNS injury.

To evaluate the safety and efficacy of stereotactic radiosurgery (SRS) compared to fractionated stereotactic radiation therapy (FSRT) for meningiomas treated over a seven year period. Of the 53 patients (15 male and 38 female) with 63 meningiomas, 35 were treated with SRS and the 18 patients with tumors adjacent to critical structures or with large tumors were treated with FSRT. The median doses for the SRS and the FSRT groups were 1400 cGy (500-4500 cGy) and 5400 cGy (4000-6000 cGy) respectively. Median target volumes for SRS and FSRT were 6.8 ml and 8.8 ml respectively. The median follow-up for the SRS and FSRT groups were 38 months (4.1-97 months) and 30.5 months (6.0-63 months) respectively. The five-year tumor control probability (TC) for benign versus atypical meningiomas were 92.7% vs. 31% (P = .006). The three-year TC were 92.7% vs. 93.3% for SRS vs. FSRT groups respectively (P = .62). For benign meningiomas, the three-year TC were 92.9% vs. 92.3% for the SRS group (29 patients) vs. FSRT group (14 patients) respectively (P = .77). Two patients in the SRS group and one in the FSRT group developed late complications. Preliminary data suggest that SRS is a safe and effective treatment for patients with benign meningiomas. Fractionated stereotactic radiation therapy with conventional fractionation appeared to be an effective and safe treatment alternative for patients not appropriate for SRS. A longer follow-up is required to determine the long-term efficacy and the toxicity of these treatment modalities.

Previously we showed that 6-hydroxydopamine lesions of the substantia nigra eliminate corticostriatal LTP and that the neuroimmunolophilin ligand (NIL), GPI-1046, restores LTP. We used cDNA microarrays to determine what mRNAs may be over- or under-expressed in response to lesioning and/or GPI-1046 treatment. Patch clamp recordings were performed to investigate changes in NMDA channel function before and after treatments. We found that 51 gene products were differentially expressed. Among these we found that GPI-1046 treatment up-regulated presenilin-1 (PS-1) mRNA abundance. This finding was confirmed using QPCR. PS-1 protein was also shown to be over-expressed in the striatum of lesioned/GPI-1046-treated rats. As PS-1 has been implicated in controlling NMDA-receptor function and LTP is reduced by lesioning we assayed NMDA mediated synaptic activity in striatal brain slices. The lesion-induced reduction of dopaminergic innervation was accompanied by the near complete loss of NDMA receptor-mediated synaptic transmission between the cortex and striatum. GPI-1046 treatment of the lesioned rats restored NMDA-mediated synaptic transmission but not the dopaminergic innervation. Restoration of NDMA channel function was apparently specific as the sodium channel current density was also reduced due to lesioning but GPI-1046 did not reverse this effect. We also found that restoration of NMDA receptor function was also not associated with either an increase in NMDA receptor mRNA or protein expression. As it has been previously shown that PS-1 is critical for normal NMDA receptor function, our data suggest that the improvement of excitatory neurotransmission occurs through the GPI-1046-induced up-regulation of PS-1.

TACH Leukodystrophy: Locus Refinement to Chromosome 10q22.3-23.1 - Volume 39 Issue 1 - Martine Tétreault, Maria Lisa Putorti, Isabelle Thiffault, Michel Sylvain, Adeline Venderver, Raphael Schiffmann, Bernard Brais, Geneviève Bernard

Aneurysmal bone cysts (ABC) are uncommon non-neoplastic expansile lesions of the bone. They usually affect long bones and vertebrae in childhood and early adulthood. Skull involvement is quite rare. Only a few cases of orbital involvement were described in the literatures. We are presenting a case of ABC that affects the orbit causing proptosis and external ophthalmoplegia. An 11-year-old girl known to have a chronic seizure disorder and school performance difficulties presented with a four month history of rapidly progressing left orbital swelling and redness. This was associated with double vision, occasional throbbing headache and feelings of nausea. The patient and her family denied any history of trauma. Her past medical and family histories were otherwise non-contributory. Physical examination revealed a left eye proptosis with mild conjunctivitis (Figure 1). She had complete left external ophthalmoplegia with pupil sparing. The left orbit was non-tender with no detectable bruit. Visual acuity in both eyes was 20/20 (right) and 20/50 (left). Fundoscopic examination revealed mild papilledema in the left eye. The rest of the physical examination was essentially normal. Computerized tomography scan of the brain revealed a left fronto-orbital expansile bony lesion with multiple cystic compartments, distorting the left orbital roof (Figure 2). The lesion pushed the eye globe laterally and externally. Magnetic resonance imaging of the left orbit confirmed that the lesion was extradural, displacing rather than infiltrating the left frontal dura, causing mass effect on the left frontal lobe.Within the lesion, the cystic components exhibited fluid-fluid levels (Figure 3 a,b,c).

An Unusual Presentation of Neurosarcoidosis in an 11-Year-Old Boy - Volume 36 Issue 6 - V. Scholten, W. M. ten Hove, E. A. Macdonald

GAB Aergic Changes in 11C-Flumazenil PET in the Drug-Naïve Stiff-Person Syndrome - Volume 40 Issue 1 - Mi-Jung Kim, Young-Min Lim, Jae Seung Kim, Kwang Kuk Kim

The purpose of this study was to evaluate the presence of headache in women with a previous history or new-onset headache during the current gestation, classify the findings, and describe the clinical characteristics and outcome of the headache. From January/1998 to June/2002 we prospectively evaluated 1101 pregnant women (12-45 years old), with a history of headache, at two prenatal clinics and an inpatient obstetric public hospital. Women were interviewed using a semi-structured questionnaire during the first, second, and third gestation trimesters and immediately after delivery. All interviews were conducted by one of the authors, using the International Headache Society Classification (IHSC-2004). In 1029 women there was a history of headache prior to the current pregnancy, 36 (3.4%) women first experienced headache during this pregnancy and 40 patients experienced new types of headache. In these 76 patients with new onset headache during pregnancy, 40 had secondary headache (52.6%), 31 had primary headache (40.8%), and 5 had headache not classified elsewhere (6.6%). According to IHSC- 2004 criteria, we found migraine in 848/1029 women (82.4%), with pregestational headache. Most of the pregnant women presented with headache, mainly in migraine, prior to pregnancy, and most of the headaches improved or disappeared during the second and third gestation trimester. In a relatively small number of pregnant women, a new type of headache started during the gestation.

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 lU/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 brother 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.

There have been many reports of percutaneous radiofrequency facet rhizotomy, perhaps better referred to as facet denervation, usually performed under general anaesthesia, with inconsistent success rates. To report the authors' outcome data using both general and local anaesthesia and to reassess the value of this controversial procedure. Our experience with 118 consecutive percutaneous radiofrequency facet rhizotomies performed on 90 patients in the Toronto Western Hospital was analyzed. Sixty percent of the procedures were performed under general anaesthesia, 40% under local anaesthesia. All patients had been temporarily virtually relieved of pain after local anaesthetic blockade of the subject facets by an independent radiologist. The patients were monitored from 1-33 (mean 5.6) months after surgery, with complete elimination or a greater than 50% subjective reduction of pain considered the criteria for success. For the first or only procedure this was 41% overall, 37% in cases done under local anaesthesia, 46% in cases done under general anaesthesia (difference not statistically significant p=0.52). There was no statistically significant difference in success rates for procedures performed in the cervical, thoracic or lumbosacral facets, with unilateral versus bilateral denervations, when two to three as compared with more than three facets were denervated, nor for operations done in patients who had had previous spinal surgery compared with those who had not. Results were not better regardless of whether hyperextension of the spine aggravated the patient's preoperative pain or not, and when the procedures were repeated in the same patient outcomes tended to be consistent, arguing against repetition of failed facet denervations. The morbidity was low, the chief problem being sensory loss and transient neuropathic pain in the distribution of cutaneous branches of posterior rami in the cervical and thoracic areas; mortality was zero. Percutaneous radiofrequency facet denervation is simple and safe, still worth considering in patients with disabling spinal pain that fails to respond to conservative treatment. The use of general anaesthesia shortens the operating time and the patient's discomfort without impairing success rate.

The Ommaya Reservoir plays an important role in a select group of neuro-oncology patients with meningeal malignancy. The benefits derived must be balanced against potential complications associated with insertion and use of the apparatus. Side effects may be minimized by careful attention to patient selection, pre-operative CAT scan (or MRI), precise surgical technique, perioperative prophylactic antibiotics and meticulous procedure during use of the reservoir.

Outpatient surgery saves the risk of nosocomial complications and health care dollars. Patients undergoing lumbar microsurgical discectomy are excellent candidates for outpatient surgery. The object of this study was to examine the feasibility of performing lumbar microdiscectomy on an outpatient protocol and to examine the potential savings associated with such a protocol. From February 1997 to September, 2001, 122 consecutive patients of the senior author were entered into a protocol of outpatient lumbar microdiscectomy. Only elective cases were considered for this study. Patients were excluded if they had significant co-morbidities, lived a significant distance out of town, or if their surgery was scheduled too late in the day. Success was defined as discharge home from the day-surgery unit approximately four hours after surgery. During the study period, 150 elective lumbar microdiscectomies were performed. Twenty-four patients were excluded based on the above criteria and four patients requested not to participate in the study. Of the remaining 122, 116 successfully completed the protocol (95.1%). Six patients were admitted from the day surgery unit; two patients with dural tears and four patients with anaesthetic side-effects. No patient was readmitted to hospital after discharge and no complications of early discharge were observed. There was a total reduction in hospitalization of 1.2 nights per elective procedure considering the 150 patients, when compared with the hospitalization times prior to outpatient lumbar microdiscectomy. Lumbar microdiscectomy can be performed safely as an outpatient procedure, resulting in a substantial reduction in hospitalization times.

A computerized analysis of 128 patients admitted with acute head injury and who underwent angiography is shown. Patients were divided into groups according to: age, sex, type of accident, state of consciousness and presence of localizing signs on admission, types of cerebral lesions on angiography, and discharge condition. There is a preponderance of young males in this series of patients, related mainly to MVA. A total of 71% of the patients had abnormal angiograms, but the incidence of normal and abnormal results did not correlate significantly with any of the chosen parameters. The same parameters were also analysed to assess their value as a prognostic index for the patient. The conclusion was drawn that the angiogram per se has no significant value as a prognostic tool, and that state of consciousness on admission is the best single index for prognosis.

Positron emission tomographic (PET) data on local cerebral metabolic rates for glucose (LCMR) are reported for 32 regions of interest (ROI)s in cross-sectional studies on 57 patients with clinically diagnosed Alzheimer's disease (AD) and 20 neurologically normal controls, and in serial studies on 13 of the AD cases, including a familial, young-onset case where the diagnosis has been confirmed at autopsy. Extensive psychological testing was done on all the AD cases. Almost all cortical regions showed a significant decline in LCMR with age in the control subjects. There were the expected cortical metabolic deficits in AD and the serial studies showed a general increase in such deficits over time in 12 of the 13 cases. The regions showing the greatest declines with time in serial studies are the same as those showing the most severe deficiencies in cross-sectional studies. The young-onset case did not show a greater rate of metabolic decline than many of the older cases studied. Results on individual psychological tests tended to correlate with metabolic rates in multiple, rather than single, cortical regions, suggesting intact neuronal networks are required for good performance. The correlations with cortical metabolic activity found were of a sign indicating that the higher the metabolic rates and the better the left:right asymmetry index, the better was the performance.

Fifteen regional cerebral blood flow studies (rCBF) were conducted on 14 patients with arteriovenous malformations (AVM). Only one patient was studied at the time of a hemorrhage. None of the patients were operated upon. All patients had angiographically demonstrated lesions. All the CT scans performed demonstrated the lesions. rCBF was increased in the involved hemisphere compared to the non-involved hemisphere and the difference was greater when the malformations were superficial. There was a higher incidence of high flow regions in the involved hemisphere of patients with AVMs compared to our normal control group and patients with subarachnoid hemorrhage (SAH) from aneurysms. Flow rates within the involved hemisphere demonstrated abnormal distributions and greater variability than normals. Some peaks previously demonstrated in the intra-arterial flow studies are not apparent using the inhalation method. This non-invasive technique has a potential to provide additional useful information on the natural history of this disorder.

Seventy six regional cerebral blood flow (rCBF) studies were conducted on 32 patients who had a total of 39 aneurysms. Twenty three of these patients were studied pre- and post-operatively. Normal values were obtained from a control group of 33 subjects, each of whom underwent one rCBF study. Flow was reduced following subarachnoid hemorrhage (SAH); it increased significantly post-operatively. Lower flows were associated with poorer clinical grades. There was a greater variation in regional distribution of flow immediately following SAH than in normals or in patients who had recovered from the acute phase. rCBF studies correlated with CT scans demonstrated that a progressive increase in ventricular size was accompanied by a progressive reduction in flow. In addition, intraventricular hemorrhage (IVH) was associated with a significant reduction in cerebral blood flow (CBF). No significant correlation between CBF and spasm was demonstrable.

The prevalence of depression in Parkinson's disease (PD) raises the issues of the difficulties of diagnosing the condition and of the relationships between depression and the natural history of the disease. A cohort of 135 consecutive patients with idiopathic PD underwent psychiatric (DSM-III-R, Goldberg depression scale), neurological (distinguishing "axial" signs from other signs of parkinsonism), and neuropsychological (particularly frontal tests) evaluations. Depression is present in more than half of the patients and it seems to be more frequent in patients with the akinetic and fluctuating forms of the disease. The subjects who are depressed do not have a greater degree of cognitive impairment, but their scores on frontal tests are higher. Moreover, the axial signs of the disease (postural instability, axial rigidity) are more severe in depressed parkinsonians suggesting a link between depression and the non-dopaminergic lesions of the disease. Even though slowness, appetite and sleep disturbances, and fatigue may be encountered in non-depressed parkinsonian patients, separation of the parkinsonian population into subgroups shows that certain symptoms are never seen in parkinsonians who are not depressed: it is thus evident that "the impression that life is not worth living", "the hopelessness", "the impression of being worthless and incompetent", "the low level of energy", "the morning sadness" are characteristic of parkinsonian depression. Parkinsonian depression has two major clinical forms. The first one is associated with a greater number of somatic manifestations: sleep disturbances, morning fatigue. corresponding to more severe depression with hopelessness and loss of self confidence. The second exhibits few somatic manifestations with apathy and slowness as frequent complaints. This study defines the symptoms of parkinsonian depression which should be better recognised in order to be treated. The link between depression and axial signs of the disease may explain why L-dopa and dopaminergic agonists improve the motor signs of depression without influencing depressive manifestations in most cases.

We have examined 138 cases of a disorder previously described in people of Portuguese origin and which has received many names. By computer analysis of 46 different items of a standardized neurological examination carried out in each patient, we have been able to delineate the main components of the clinical presentation, to conclude that the marked variability in clinical expressions does not negate the homogeneity of the disorder, and to describe the natural history of this entity which should be called, for historical reasons, “Machado-Joseph Disease”. This hereditary disease has an autosomal dominant pattern of inheritance, presenting as a progressive ataxia with external ophthalmoplegia, and should be classified within the group of “ Ataxic multisystem degenerations ”. When the disease starts before the age of 20, it may present with marked spasticity, of a non progressive nature but often so severe that it can be accompanied by “Gegenhalten” countermovements and dystonic postures but little frank dystonia. There are few true extrapyramidal symptoms except akinesia. When the disease starts after the age of 50, the clinical spectrum is mostly that of an amyotrophic polyneuropathy with fasciculations accompanying the ataxia. For all the other cases the clinical picture is a c.ontinuum between these two extremes, the main determinant of the clinical phenotype being the age of onset and a secondary factor, the place of origin of the given kindred. The ataxic and amyotrophic components are clearly progressive with time in contrast to the spasticity component. Although the majority of known cases are of Portuguese origin, this is not obligatory. The next research endeavour should be a search for the chromosomal site of the gene, using molecular biology technology such as those for recombinant DNA.

Two additional patterns, minuscule 28 per second positive spikes and huge N-shape potentials, have been identified exclusively in the EEGs of patients with 14 and 6 per second positive spikes. They occur predominantly during drowsiness and light sleep, usually in children, seldom in young adults. Their presence adds little to the clinical relevance of positive spikes. Familiarization with the N-shape potentials--the commoner of the two patterns--is important, lest they are mistaken for interictal abnormalities of significance such as atypical spike-wave complexes.

The effectiveness of indomethacin treatment (1 mg/kg) as an antipyretic was tested in patients after cranial trauma or brain surgery involving the centromedial forebrain. Indomethacin was effective in reducing temperature in 10 of 11 cases which showed a dipyrone-resistant hyperthermia developing in the first 24 hours after brain damage, while no significant antipyretic effect was seen in hyperthermic cases developing more than 72 hours after cranial trauma or brain surgery. Biochemical tests estimating the effect of indomethacin, and pyrazolone derivatives on the arachidonic acid metabolism showed significant effects of indomethacin only in influencing cyclooxygenase activity and no effect of any drugs on lipoxygenase actions. In view of these observations, the use of indomethacin is recommended as a treatment for neurogenic hyperthermia.

Most studies of third nerve palsy (TNP) antedate computerized imaging and focus primarily on chart review of referral outpatients. To compare a large contrasting population, I reviewed 1400 personally-examined municipal hospital inpatients with TNPs seen over 37 years. TNPs were bilateral in 11%, complete in 33%, without other neurological signs (isolated) in 36%, and associated with recurrent cranial neuropathies in 7%. Third nerve damage occurred in the subarachnoid space in 32%, the cavernous sinus in 23%, the brainstem in 14%, as a nonlocalized peripheral neuropathy in 18% and at an uncertain location in 13%. Causes were trauma (26%), tumor (12%), diabetes (11%), aneurysm (10%), surgery (10%), stroke (8%), infection (5%), Guillain-Barre and Fisher syndromes (5%), idiopathic cavernous sinusitis (3%), benign self-limited (2%), miscellaneous (4%), and unknown (3%). Local causes, besides an abundance of trauma, included six cases involving cysticercosis, four with wound botulism, and one with coccidiomycotic meningitis. Of 234 patients with diabetes, microvascular ischemia was the cause of TNP in only two-thirds (five had aneurysms) and 53% of those with diabetic microvascular ischemia had pupillary involvement-often bilateral, suggesting concomitant autonomic neuropathy. Only 2% of aneurysms spared the pupil. Apainful onset occurred with 94% of aneurysm and 69% of diabetic cases. Bilateral TNPs, multiple cranial neuropathies, and accompanying neurological signs were common among our inpatients, as were causes rare in outpatient settings such as severe trauma, transtentorial herniation, midbrain strokes, and the Guillain-Barre syndrome. Few cases remained undiagnosed and nondiabetic ischemia was rare.

Zonisamide (ZNS) is an antiepileptic drug developed in Japan. Various experimental studies have investigated the effects of ZNS. However, the mechanism of action of ZNS against limbic seizures and secondary generalization is not well-known. We studied ictal regional accumulation of ZNS in the rat brain during kainic acid (KA)-induced limbic status epilepticus. Fourteen male Wistar rats underwent a stereotactic operation. For recording the electroencephalogram (EEG), electrodes were placed in the left amygdala (LA), left dorsal hippocampus, and over the left sensorimotor cortex. For microinjection, a stainless steel cannula was also inserted into the LA. Seven days after surgery, rats were anesthetized and a catheter was inserted into the femoral vein. The animals were immobilized and allowed to recover from anesthesia for at least two hours. In eight rats, 1.0 microL (1.0 microg) of KA was injected into the LA, and 1.0 microL of phosphate buffer solution was injected into the LA in six control rats. Sixty minutes after injection, 14C-ZNS was administered intravenously, and an autoradiographic study was done. During limbic status epilepticus, only seizures in the sensorimotor cortex were markedly attenuated a few minutes after 14C-ZNS administration. Additionally, high uptake of 14C-ZNS was noted ipsilaterally in the sensorimotor cortex, parietal cortex and thalamus (lateral portion). In control rats, no EEG change was seen, and distribution of 14C-ZNS was rather homogeneous. These results suggested that ZNS suppresses secondary generalization of limbic seizures by a direct effect on the cerebral cortex.

Background: The current methods to predict recurrence and aggressive behaviour of meningiomas rely mainly on histological grading, histological subtype, proliferative index, as well as brain invasion. In many instances, histological grade alone fails to predict recurrence in the grade I and grade II meningiomas. Deletions of 1p and 14q have previously been reported to correlate with poor prognosis in terms of either recurrence or higher histological grades. The Her2neu (ErbB2) amplification has been shown to be a useful predictor of aggressive behaviour in breast and ovarian tumours, but its significance in meningioma is so far uncertain. Method: In order to determine the cytogenetic differences between 22 recurrent and 25 non-recurrent meningiomas of all grades, we used fluorescent in situ hybridization (FISH) DNA probes for 1p36, 14q11.2 and 17q11.2-12 (Her2neu) on formalin fixed paraffin embedded (FFPE) tissue from the Brain Tumour Tissue Bank (BTTB), London Health Science Center (LHSC). Results: We showed a positive association for meningioma recurrence correlated with 1p36 deletion plus or minus 14q 11.2 deletions in all grades of meningiomas. The Her2neu amplification was strongly associated with 1p/14q co-deletion in cases of recurrent meningiomas, especially the higher grade tumours. Conclusion: These cytogenetic markers can be applied in addition to histological grading for predicting the risk of recurrence and biological behaviour.

Few data are available about the diagnostic yield of the lactate stress test (LST) in a large group of patients with mitochondriopathy (MCP). Serum lactate was determined once before, three times during, and once after a 15-minute, constant 30W workload on a bicycle in 62 controls, aged 17 to 84 years, 155 patients with MCP, aged 17 to 87 years, and 31 patients with neurological disorders other than MCP. Lactate's upper reference limits at rest, 5, 10, 15 minutes after starting, and 15 minutes after finishing the exercise were 2.0, 2.1, 2.1, 2.1 and 1.8 mmol/l respectively. The test was regarded abnormal if more than two of the five lactate values exceeded the cut-off levels. Among the 103 patients with abnormal LST, 64 (62 %) had normal resting lactate. The sensitivity of the test was 67% and the specificity 94%. The LST proved to have a high sensitivity and specificity in the detection of patients with MCP, being thus a simple but powerful tool to assess the impaired oxidative metabolism in MCP patients.

Symptomatic (secondary) dystonias associated isolated lesions in the brain provide insight into etiopathogenesis of the idiopathic form of dystonia and are a basis for establishing the possible correlation between the anatomy of a lesion and the type of dystonia according to muscles affected. In 358 patients with differently distributed dystonias, a group of 16 patients (4.5%) was encountered in whom dystonia was associated with focal brain lesions. Of the 16 patients, 3 patients had generalized, 3 segmental and 4 hemidystonia, while the remaining 6 patients had focal dystonia. The most frequent etiologies were infarction in 7, and tumor in 4 patients. These lesions were usually found in the lenticular and caudate nucleus, thalamus, and in the case of blepharospasm in the upper brainstem. Our results support the suggestion that dystonia is caused by a dysfunction of the basal ganglia.

Focal gliomas involving the midbrain tectum and tegmentum have been identified as having a better prognosis than diffuse tumors affecting the brain stem. However, only limited information is available concerning treatment effectiveness and long term outcome for these patients. A retrospective, population-based cancer registry survey was performed to assess the clinical features and treatment courses of patients with focal midbrain tumors. Sixteen patients with midbrain gliomas were identified; eight had tectal gliomas and eight tegmental gliomas. Thirteen patients presented with symptoms related to hydrocephalus, and 12 required a ventriculoperitoneal shunt. Seven patients underwent surgery directed at the tumor. Eight patients underwent initial radiation therapy and none had initial chemotherapy. One patient diagnosed at age 18 months had a rapidly growing tumor after 14 months of follow up which has responded to chemotherapy. The mean survival of this patient population was 84 months (range 3-280 months) after diagnosis, with only one tumor related death occurring (280 months after diagnosis). Survival was not affected by tumor location within the midbrain (tegmental or tectal) or by whether radiation therapy was or was not administered. Patients with focal midbrain gliomas require symptom control aimed at treatment of hydrocephalus, or mass effect from the tumor. However the extended survival of this population suggests that routine aggressive surgical debulking is often not required. Furthermore, the routine use of radiation therapy or chemotherapy for all such patients is questioned.

Studies of sporadic malignant gliomas have identified structural abnormalities in a number of chromosomal regions, especially losses of DNA on 9p, 10 and 17p. We undertook the following molecular analysis in families with glioma to determine the frequency of chromosomal losses in these regions and to test the utility of microsatellite markers in demonstrating losses of heterozygosity. Genomic DNA was extracted from tumor tissue and venous blood from 20 patients with a family history of glioma. Dinucleotide repeat polymorphisms (microsatellites) were analyzed by polymerase chain reaction to assess loss of constitutional heterozygosity (LOH) on 9p, 10 and 17p. Three polymorphic markers on chromosome 9 (D9S104, D9S161, D9S165), one on chromosome 10 (D10S209), and two on 17p (D17S786, D17S796) were used. Autoradiographic films were analyzed for LOH after radioactively labelled polymerase chain reaction products were resolved on denaturing formamide-acrylamide gels. Of 20 patients informative for at least one of three chromosome 9 markers, 12 (60%) showed LOH at one or more loci; of 9 informative for the chromosome 10 marker, 4 (44%) showed LOH; and of 16 informative for at least one of two chromosome 17 markers, 7 (44%) showed LOH at one or both loci. These LOH rates do not include instances of tumor nullizygosity (0-35%) and therefore represent minimum frequencies of chromosomal losses at these loci. Microsatellite markers can be used to detect LOH in archival glioma tissue. As in sporadic gliomas, frequent LOH was observed on 9p (9p21-22), 10 and 17p, supporting the notion that these regions may harbour tumor suppressor genes important in glioma development. Further work will be required to determine whether the proportion of LOH in these chromosomal regions is higher in familial gliomas than sporadic ones, as might occur with an inherited suppressor gene conferring susceptibility to gliomas in families.

Re: Triphasic Waves versus Nonconvulsive Status Epilepticus: EEG Distinction. Can J Neurol Sci 2006;33:175-80 - Volume 33 Issue 4 - José L. Fernández-Torre

The aim of the present study was to examine the frequency and the phenotypic manifestations in a French-Canadian population with a chromosome 17p11.2 duplication (Charcot-Marie-Tooth type 1A, CMT-1A). Molecular analysis were performed by Southern blot using pVAW409R3a probe. Clinical evaluation was carried out according to the scale defined by the European HMSN Consortium. The frequency of duplication was found to be similar in the adult (70.8%) and pediatric (72.7%) populations. Onset of symptoms occurred before 20 years of age in 85.7% of adult cases and before the age of 5 in 80% of the pediatric cases. The classical CMT syndrome was observed in 77% of the cases and the syndrome was associated with additional features in 15% of cases in the adult population. All the children presented with classical CMT syndrome with no additional features. There was a significant correlation between the disability score and the duration of the disease but no correlation was found between median nerve conduction velocity and the functional handicap, the age at onset or the duration of the disease. In one family, there was a very conspicuous anticipation over five observed generations. This study reveals that the age at onset, the clinical and electrophysiological variability as well as the functional disability variations in a French-Canadian population did not differ from those reported in other populations.

A 17th century B.C. Surgical Papyrus known as "The Edwin Smith Papyrus" was published in facsimile and hieroglyphic transliteration with translation and commentary by James Henry Breasted in 1930. The Papyrus was acquired by Edwin Smith in Luxor, 1862. This document was conceived in the Pyramid Age (3000-2500 B.C.) and remains in material form from the 17th century B.C. It is of importance to the history of Neurology as it contains the earliest mention in oriental literature of (a) the brain and meninges (b) calvarial and cervical vertebral injuries in details of pathology, symptomatology, treatment and prognosis and (c) functional localization in the brain and spine. Most importantly, Papyrus Smith is a statement of the medical ethic of its time.

In 1665 the Danish scholar Niels Stensen (1638-1686) reached Paris, where he pronounced a discourse on brain anatomy that was to orient neuroscientists for years to come. In his lecture, Stensen rejected ancient speculations about animal spirits and criticized René Descartes and his followers who, despite a poor knowledge of brain anatomy, elaborated complex models to explain the multifaceted function of what he considered the principal organ of the human mind. He advocated the need for studying the brain through a comparative, developmental and pathological convergent approach and called for appropriate dissection methods and accurate illustrations. His own careful anatomical studies permitted him to precisely depict many brain structures. After pioneering works in paleontology and geology, he devoted himself to theology. In 1677 Stensen converted from Lutheranism to Catholicism and, while working relentlessly as a bishop and apostolic vicar in Northern Europe, he died in self-imposed poverty at age 48.

A questionnaire survey has been made of the life effects of narcolepsy in 180 patients, 60 each from North American, Asian and European populations, with 180 similarly distributed age and sex matched controls. Life-effects were attributed by the patients to the primary symptoms of excessive daytime drowsiness, sleep attacks, cataplexy, vivid hypnagogic hallucinations and sleep paralysis, and also to other frequent symptoms such as visual problems (blurring, diplopia) and memory impairment. Occupational problems were prevalent (over 75%) and included statistically significant deleterious effects upon performance, promotion, earning capacity, fear of or actual job loss and increased disability insurance. Driving was greatly affected and patients fell asleep at the wheel more frequently (66%), had near or actual accidents from drowsiness or falling asleep at the wheel (67%), and could experience cataplexy (29%) or sleep paralysis (12%) while driving. Work or home accidents attributed to sleepiness or sleep (49%) or related to smoking (49%) were much more common in patients. There were also deleterious effects on education, recreation and personality related to disease. Narcolepsy can produce a variety of life-effects probably more serious and pervasive than, for instance, those of epilepsy, therefore emphasizing the importance of early diagnosis and treatment.

The medical profession's modern quandaries with Multiple Sclerosis (MS) largely began in 1849, with Friedrich von Frerichs' (1819-1885) early description of the clinical and pathological features of what he termed Hirnsklerose ("brain sclerosis"). This manuscript is an overview of the century of research (1850-1950) that followed the emergence of this clinical entity, with a focus on the hitherto under-explored English Canadian perspective. Using journal articles, reviews, and case studies, this historiographical paper reviews what may be some of the earliest recorded cases of MS in Canada, and outlines the diagnostic challenges that confronted early Canadian physicians in their encounters with MS. Early Canadian attempts to characterize the aetiology and epidemiology of MS and treat it are also discussed. These activities were influenced by developments in the field in Europe and the United States, and helped set the stage for the modern era of immunologic and therapeutic research on MS.

We present clinical and pathologic data on four previously unreported familial ALS pedigrees and review and analyze by descriptive and exploratory statistical techniques all published cases of familial ALS (1850-1989). In contrast to the age-dependent incidence of sporadic ALS, the age of onset of familial ALS is normally distributed about a mean of 45.7 years (std. dev. 11.3 years). Survival curves for the familial ALS data also demonstrate a skewed distribution with a median survival time of 24 months with 74% surviving at 12 months, 48% at 24 months and 23% surviving at 60 months. The patient characteristics of age at onset of disease, sex and focus of disease onset are unrelated variables and age at onset of disease is the only predictor of survival (Cox's proportional hazard model, chi-square 14.74, p = 0.0001). By applying accelerated failure time models with a log-normal baseline distribution, estimated probabilities for survival adjusted by age at onset were calculated. It was found that the older the age at disease onset, the shorter the survival.

The general principles of bypass surgery as they affect the cerebral circulation are reviewed. The preliminary results of an extracranial intracranial bypass operation performed on a group of 19 patients suffering from cerebral ischemia are presented. The results of the surgery compare favorably with those published in the literature.