Huntington’s Disease (HD) is a progressive degenerative disorder of the central nervous system inherited as an autosomal dominant trait. Clinically, the disorder is characterized by choreoathetosis (with age of onset typically in the late thirties or early forties) and neuropsychiatric disturbance. The striatum is particularly vulnerable to the degenerative disease process, with selective loss of medium spiny neurons and decreased levels of associated neurotransmitters, including substance P, GABA, met-enkephalin and dynorphin. Although the underlying pathophysiology is unknown, recent theories concerning pathogenesis have involved mitochondrial abnormalities and excitotoxin-mediated damage. The gene for HD has recently been discovered and characterized as an unstable CAG trinucleotide repeat sequence on the short arm of chromosome 4 (now known as IT 15). The direct test now available for the HD gene has facilitated disease diagnosis, particularly for those with unclear family history or chorea of uncertain origin; presymptomatic testing is also available. Management of affected individuals is unsatisfactory as only symptomatic control is available. However, as the effect of the genetic abnormality may soon be known, specific treatment of the disorder may become available in the near future.

Of 112 stereotactic high-activity iodine-125 implants for malignant brain tumors done as of July 1, 1994, ten have been done for recurrent single brain metastasis and constitute the study group described herein. All patients had initially undergone craniotomy for tumor resection followed by fractionated external beam whole brain radiation and recurred at the same site in the brain. The interval between initial cancer therapy and occurrence of the brain metastasis was 13 – 156 weeks (median: 63 weeks). The interval between initial treatment of the brain metastasis and its recurrence treated with brachytherapy was 13-69 weeks (median: 35 weeks). Minimum brachytherapy dose administered was 70 Gy at a median dose rate of 67 cGy/hour. Eight- patients have died. Two died suddenly at 2 and 13 weeks post-implant of presumed pulmonary embolus. Five died of recurrence of the brain metastasis at 20, 39, 52, 103, and 143 weeks post-implant, and one died of systemic metastases at 40 weeks post-implant. Two patients remain alive 183 and 324 weeks post-implant. High-activity iodine-125 brachytherapy appears to be of benefit for selected patients with recurrent single brain metastasis but larger, and preferably randomized studies are needed.

A prospective trial to demonstrate the efficacy of intrathecal baclofen therapy by implanted pump for adults with spasticity due to spinal cord injury or multiple sclerosis was initiated in our hospital. Of the 140 patients assessed, 7 met the following criteria for inclusion in the study: a modified Ashworth score > 3, a spasm frequency score > 2, and an inadequate response to oral antispasticity drugs, (i.e., baclofen, clonidine and cyproheptadine). All patients responded to intrathecal bolus injection of baclofen in the double blind, placebo-controlled screening phase (mean bolus dose = 42.8 μg). Programmable Medtronic pumps were implanted in 4 patients while 3 patients received nonprogrammable Infusaid pumps. Post-implantation, a marked decrease in spasticity occurred with a significant reduction of the Ashworth score (mean = 1.8, p < .005), a reduced spasm score (mean = 0.8, p < .005), and an improved leg swing in the pendulum test. These effects were maintained during a follow-up of 24 – 41 months (average infusion dose = 218.7 μg/day). The gross cost-savings due to reduced hospitalizations related to spasticity was calculated by comparing the cost for the two year period before pump implantation to the same period after treatment for 6 of the 7 patients. The cost of in-hospital implantation as well as the cost of the pumps were deducted from the gross savings. There was a net cost-saving of $153,120. Our findings agree with the reported efficacy and safety of intrathecal baclofen treatment, and illustrate the cost-effectiveness of this treatment.

Background: Asymptomatic cerebral aneurysms are diagnosed more frequently since the advent of computed tomography and magnetic resonance imaging. Their management is currently empirical. We have used decision analysis to place it on a more analytical basis. Methods: Decision analysis was used to determine the benefit in years of survival free of sequelae resulting from elective surgery of unruptured aneurysms over natural history. We took 2% as the annual rate of rupture (r), 73% as the risk of death or disability with rupture (M), and 6.5% for the average risk of elective surgery (S). Benefit was calculated from the equation L{[1-(1-r)L]M/2-S} [1] for life expectancy (L) corresponding to each quinquennial age group from age 15 to 100 years. Sensitivity analysis was performed to take into account increasing risk of elective surgery based on the size, and accessibility of the aneurysm, and variable risks of rupture and outcome. Results: A gain of at least one year of survival free of neurological sequelae is achieved by surgery compared to natural history for patients whose life expectancy is 19.5 years, corresponding to age 63.5 years for males and 68 years for females. The life expectancy at which a benefit accrues is longer (the patient is younger) for larger, less accessible aneurysms, for lower rates of rupture, and for lesser risks of death or disability from rupture. Conclusions: Elective surgery of unruptured asymptomatic aneurysms achieves an increased survival over the natural history of at least one year free of neurological sequelae in patients whose life expectancy is 19.5 years or more, using our baseline assumptions. Using equation [1], the corresponding life expectancy producing this benefit can be calculated to account for the increased surgical risk of large, poorly accessible aneurysms and for factors affecting natural history.

The descending motor tracts were activated using a high voltage electrical stimulation technique at four levels: the motor cortex, brainstem (around the pyramidal decussation), and the first and sixth thoracic vertebral levels (Tl, T6). Electromyographic activity was recorded from the tibialis anterior or extensor digitorum brevis muscles. Consistent motor action potentials could be evoked in all normal subjects. The conduction velocity of the descending tracts was estimated to be 62 to 79 m/s. The sum of synaptic delay and utilization time at the motoneurons (spinal delay time) was estimated to be 0.5 ± 0.3 ms indicating a mono- or oligosynaptic connection. In patients with diffusely affected descending tracts, the technique showed slowed conduction along the descending tracts and prolonged spinal delay time which may include the time required for temporal summation of excitatory postsynaptic potentials as well as synaptic delay and utilization time. In patients with a localized lesion, localized conduction delay was found at the appropriate segment.

Distal sensory peripheral neuropathy (DSPN) has been reported in 5 to 75% of patients with human immunodeficiency virus (HIV) infection, particularly in advanced stages of the disease. Twenty HIV seropositive patients were studied prospectively to determine the frequency of DSPN in clinical stage II and III of the HIV infection, and to investigate the role of vitamin B12 deficiency on the frequency of DSPN in HIV patients. All patients had complete blood count, serum vitamin B12 level, anti-intrinsic factor antibody, Schilling test, and electrodiagnostic studies including nerve conduction studies and concentric needle examination in the lower extremities, and sympathetic skin responses. Only 1 patient (5%) had clinical and electrophysiological evidence of possible DSPN. Of the 6 patients with abnormal Schilling test, only one had DSPN based on distal sensory symptoms, abnormal neurological examination and electrodiagnostic studies. Evidence for possible DSPN was present in 5% of patients with early HIV infection and did not appear to be more frequent in patients with concurrent vitamin B12 deficiency.

The prognosis and methods of treating headaches were studied in a group of children, 10 years after their initial diagnosis in 1983. Follow-up was achieved for 77 patients (81%). Headaches persisted in 72.7% but were much improved in 81.3%. Medication use was uncommon, with non-prescription medications used by 30.3% and prescription medications by only two. These data suggest that although childhood onset headaches are likely to persist, children who receive early education regarding the use of non-pharmaceutical methods of headache control appear to rely on these methods even after an interval of 10 years.

An 18-year-old man was treated from birth with chronic high dose pyridoxine (vitamin B6) up to 2000 mg per day for pyridoxine-dependent seizures. Within two years of onset of treatment, he developed a sensory neuropathy which did not progress over the following 16 years. Electrophysiological studies were consistent with a pure sensory neuronopathy expressed as centripetal degeneration of processes of the dorsal root ganglion cells.

A man with acquired immune deficiency syndrome suddenly developed bilateral complete ptosis and minor vertical gaze limitation. Magnetic resonance imaging revealed a lesion in the midbrain surrounding the sylvian aqueduct in addition to bilateral masses in the caudate nuclei. Pathologic examination showed that the caudate lesions were central nervous system lymphoma of B cell origin, but the midbrain lesion contained only signs of AIDS encephalopathy. The periaqueductal lesion involved the caudal central subnucleus and probably also the subnuclei of the superior and inferior recti of the oculomotor nuclear complex bilaterally.

We report bilateral temporal lobe MRI findings in a patient following an episode of prolonged hypoglycemia uncomplicated by coexisting anoxia, hypotension, acidosis, drug intoxication, infection, or status epilepticus. The MRI findings are discussed in relation to the experimental and human data on hypoglycemic neuronal injury.

Writer’s cramp is frequently associated with hand tremor and with other focal dystonias. Sometimes brain infarction, haemorrhage, arterio-venous malformations or tumors are found to cause symptomatic focal dystonias. A 44-year-old man came to our attention due to writer’s cramp of his right hand and postural 6-8 Hz tremor. About three months after the onset of the disease the tremor and dystonia disappeared, while a right hemiparesis gradually appeared. Cranial computed tomography showed a hypodense nonhomogeneous lesion in the left cerebral hemisphere parietally, that was assumed to represent a cystic tumor. The patient underwent craniotomy and the histological diagnosis revealed an astrocytoma (Grade II-III). In conclusion our findings confirm the common anatomical basis of symptomatic focal dystonia and tremor. Both can appear after disruption of the pathways within and adjacent to the basal ganglia.

The magnitude of the problems faced by Canadian society as a result of an aging population has been identified. Perhaps the most important concern related to this greying of Canada is the increasing incidence of dementia and Alzheimer’s disease. Therapeutic options for these disorders have been limited to date. Advances in biotechnology and molecular biology will offer novel approaches to treatment. These and the expansion of more traditional therapeutic avenues require guidelines with the aim of optimizing their development.