Contrast enhancement on computerized tomography (CT) scans has been used in directing therapy for presumed intracranial gliomas. However, for moderately anaplastic astrocytomas (MOAAS) and highly anaplastic astrocytomas (HAAS), it provides no information about proliferative potential. The bromodeoxyuridine (BUDR) labeling index (LI), however, indicates proliferative potential, correlating with histologic malignancy and survival. An LI < 1% is a favorable indicator; LI > 5% suggests more aggressiveness. To determine the correlation, if any, between BUDR LI and contrast enhancement, CT scans of 71 patients with cerebral hemisphere tumors labeled with BUDR were retrospectively reviewed. Among 36 MOAAS, the BUDR LI was < 1% in 77% of enhanced tumors and 61% of unenhanced tumors. Among 35 HAAS, it was < 5% in 56% of enhanced tumors and 90% of unenhanced tumors. Therefore, contrast enhancement on CT scans does not always correctly predict proliferative potential in these tumors, and biopsy and labeling studies are recommended before therapy.

A 15-year experience with paraneoplastic sensory neuronopathy at the Mayo Clinic is reviewed. Of 26 patients with paraneoplastic sensory neuronopathy, 19 had small cell lung cancer, 4 had breast cancer, and 3 had other neoplasms. There was a striking predominance of females (20:6). Neuropathic symptoms (pain, paresthesia, sensory loss) were asymmetric at onset, with a predilection for the upper limbs; in three patients, symptoms were confined to the arms. Electrophysiologic testing revealed absent sensory responses and normal or minimally altered motor responses. Slightly more than half the patients had associated autonomic, cerebellar, or cerebral abnormalities. In some patients, treatment of the neoplasm seemed to halt progression of the neuronopathy, but none had neurologic improvement and most continued to worsen, even when the oncologic response was good. Distinguishing between paraneoplastic and nonparaneoplastic sensory neuronopathies can be difficult, but prominent neuropathic pain, neurologic dysfunction involving more than the peripheral sensory system, or an increased cerebrospinal fluid protein value should prompt a careful search for a cancer.

Abiotrophy is hypothesized to explain the onset and time course of deficits in Parkinson’s disease (PD) Abiotrophy includes: 1) exposure to agent(s) causing the death of dopaminergic nigrostriatal neurons (DNSns), 2) gradual death of DNSns with age, 3) summation of 1) and 2) until DNSn numbers fall below a threshold for detectable neurological deficits. Murine DNSn death following methyl-phenyl-tetrahydropyridine (MPTP) exposure occurs according to an exponential relationship while age-related death of DNSns occurs according to a second exponential relationship. Summing the two exponential losses overestimates experimental DNSn death showing a simple abiotrophic model is not sufficient. Aged murine DNSns greatly increase their dopamine synthesis and the density of their striatal axon terminals which may explain the above threshold. Murine DNSns die gradually after MPTP exposure and L-deprenyl treatment rescues MPTP-damaged DNSns by a previously undiscovered action, altering the abiotrophic interactions and possibly explaining the slowed progression of PD found with deprenyl treatment.

A group of six subjects with intractable spinal spasticity completed a double-blind cross-over paradigm in which they received two intrathecal bolus injections of baclofen solution five hours apart on two different days and two intrathecal bolus injections of placebo saline five hours apart on two other days. Each subject was repeatedly tested with a battery of clinical and physiological tests. In contrast to the placebo injections, the group responded to the baclofen injections with subjective and objective, clinically significant improvement in parameters of spasticity in their lower limbs, including muscle tone, frequency of spasms, hyperreflexia and passive range of joint motion. Furthermore, this improvement was maintained following thirty consecutive days of intrathecal bolus injections of baclofen at a fixed dose.

Many HIV-infected children have neurological involvement. We present our observations in 49 cases, 58% of which had some form of clinical neurological impairment. Most of the patients affected (71%) presented with progressive encephalopathy, characterized by developmental delay with loss of acquisitions and cognitive decline, an impaired growth curve, microcephaly and corticospinal dysfunction. CT-scan imaging shows cerebral atrophy in all cases and basal ganglia calcifications in 29%. Non-specific abnormalities are found on the EEG in two-thirds of cases and in the CSF in slightly less than half the cases. Pathological studies sometime revealed HIV encephalitis or lateral corticospinal tracts degeneration. Neurological impairment secondary to vascular events, neoplasms or opportunistic infections were rare, especially when compared with the adult HIV population.

Eight cases of basal skull fracture with transverse fracture of the petrous temporal bone with medial extension to the internal carotid artery and lateral extension of the structures of the middle ear are described. Injuries in all cases were due to major blunt impact to the head usually occurring in a motor vehicle accident. General autopsy revealed major blood loss without any obvious external or internal site of hemorrhage suggesting that exsanguination was a complication of the head injury. The internal carotid arteries at the most medial extension of the fractures were lacerated or transected in all cases. In selected cases, the cervical internal carotid arteries were perfused and perfusate escaped rapidly from the ear(s) with the majority of fluid bypassing the cerebral venous system. Magnetic resonance image reconstruction of sequential sections of the fractured base of the skull confirmed the laceration of the internal carotid arteries and disruption of the middle ear. Based on this evidence, we propose that some displaced fractures of the base of the skull produce carotid-middle ear continuities which act as arterial shunts, resulting in rapid fatal exsanguination through the ear.

Levodopa-induced dyskinesia, one of the most frequent long-term side effects of antiparkinsonian therapy, is often attributed to denervation supersensitivity of dopamine receptors and perhaps more specifically the D-1 receptor. The available evidence based not only on clinico-pathological studies in patients but also on results of experiments performed on methyl-phenyl-tetrahydropyridine (MPTP)-treated monkeys suggests that the mechanisms may be more complex than heretofore believed. Thus it appears that no single receptor is the sole culprit, that some form of denervation supersensitivity is probably involved but not in the form of increased density of dopamine receptors. Moreover, other neurotransmitter systems must be considered such as GABA, excitatory aminoacids and peptides. The MPTP monkey model remains very useful for predicting the potential of new drugs for inducing dyskinesia. Such trials however must be performed in drug-naive animals.

Previous studies have failed to provide serological evidence to incriminate a retroviral infection in the cause of multiple sclerosis. Gene amplification techniques have also failed to identify retroviral footprints in DNA from peripheral blood leukocytes. Here we provide evidence that proviral DNA of HTLV-I and HTLV-II is not found in the central nervous system tissues of patients with multiple sclerosis, patients with amyotrophic lateral sclerosis and controls.

Despite the great capacity for the pediatric brain to recover from stroke, the morbidity and mortality in children who harbor an arteriovenous malformation (AVM) remains high. This study examines the clinical data and management experience with 132 patients with brain AVM from 1949 to 1989. Although the high tendency for a childhood AVM to present with hemorrhage (79%) remained constant for the forty year study period, the associated morbidity and mortality of hemorrhage changed. The mortality rate from hemorrhage for the entire series was 25%, which was reduced from 39% to 16% after the introduction of computed tomography. The mortality from AVM hemorrhage since 1975 was dependent on location; 8 of 14 patients (57%) with a cerebellar AVM died from hemorrhage while only 2 of 44 patients (4.5%) with a cerebral hemisphere AVM died (p < 0.0001). Sixteen children (12%) presented with a chronic seizure disorder. Surgical excision of the malformation resulted in complete seizure control off anti-convulsant medication in 73% of patients. Although 21% of patients were treated non-operatively (many with terminal poor-grade hemorrhage), 79% had a surgical procedure with total AVM excision achieved in 70 patients (53.1%). Complete AVM resection was followed by a normal neurological outcome in 47 children (67%). Most partial excisions (n=9) and clipping of feeding arteries (n=7) were performed in the early years of this study, and did not provide protection from rehe-morrhage. Although conservative management has been advocated for selected non-hemorrhagic AVMs, we conclude that essentially all children with an AVM should be treated in order to eliminate the risk of hemorrhage. Long-term conservative management in pediatric patients is warranted only in patients with large AVMs not amenable to treatment using current multimodality techniques.

The purpose of this study was to explore further the hypothesis that changes in cognitive function may occur in the mild stages of multiple sclerosis (MS) by determining whether ventricular enlargement was related to cognitive function. Ten measures of ventricular size were made in a sample of 123 MS patients with mild disability and 60 well-matched healthy controls. In addition, sixteen tests of cognitive function and the Beck Depression Inventory were administered. For the MS group, there were significant correlations between the ventricular measures and cognitive performance but not for the normal controls. Scores on the Beck Depression Inventory were not correlated with either cognitive performance or ventricular enlargement. These findings suggest that for the MS group cognitive impairment was related to the disease process but not to the level of depression.

Recent observations indicate that antibodies to gangliosides are found in many patients with amyotrophic lateral sclerosis (ALS). If antigen-antibody complexes occur in ALS, elevations of cytokine levels might be expected, among them the cytokine interleukin-6 (IL-6). IL-6 is secreted by activated monocytes and other cell types and is an important mediator of the inflammatory response. We have measured cerebrospinal fluid (CSF) IL-6 levels in patients with ALS and compared them with those in psychiatric and neurodegenerative disorders not believed to be due to immune disorders of the central nervous system. We found no significant differences in CSF IL-6 levels between these groups.

Vitamin E (d-α-tocopherol) has proven to be a useful adjunct to anticonvulsant drugs in clinical studies. Improvement has occurred even in patients with complex partial seizures, which are often resistant to drug therapy. In animals, vitamin E is effective against ferrous chloride seizures, hyperbaric oxygen seizures and penicillin-induced seizures. It has failed, however, to show anticonvulsant effects in the standard animal models used for drug screening – the maximal electroshock and threshold pentylenetetrazol tests. The present experiments were designed to further explore the anti-epileptic actions of vitamin E in animals. Three models related to complex partial epilepsy were used: 1) the development of amygdala-kindled seizures; 2) the development of electrically-induced status in kindled animals; and 3) the development of kainic-acid seizures. Vitamin E failed to produce significant effects in any of the models.

Positron emission tomography (PET) allows the study of physiological and neurochemical processes which would otherwise be inaccessible, using radioactive labels on biological compounds to follow their fate in the body. By analysing changes of concentration with time we can measure blood flow, neuronal metabolism and receptor ligand interactions. In Parkinson’s disease (PD), PET has been used to examine the dopaminergic deficit and its relationship to motor performance. It has also been shown to detect asymptomatic dopaminergic lesions that have implications for the etiology of PD. In untreated PD there is increased density of D2 binding sites, while in chronically treated PD with motor fluctuations, D2 receptor density is reduced. [18F]-fluorodeoxyglucose studies of demented PD patients show a pattern of cortical metabolism similar to Alzheimer’s disease. Activation studies, which measure changes in blood flow during the performance of motor tasks, show reduced activation of medial frontal areas in PD.

Recent evidence has suggested a potential role for involvement of excitatory amino acids (EAA) in the pathogenesis of the neuron loss in motoneuron diseases. We have examined the ability of an antagonist of N-methyl-D-aspartate (NMDA) receptors to halt or retard the progression of neurological symptoms in a murine form of motoneuron disease. The wobbler mouse is an autosomal recessive mutant which develops progressive neurological symptoms secondary to motoneuron loss. Treatment of wobbler mice with the NMDA receptor antagonist (+)-5-methyl-10,l 1-dihydro-5H-dibenzo(a,d)cyclohepten-5, 10-imine maleate (MK-801) did not retard neurological deterioration as assessed by a semiquantitive clinical scale. We conclude that NMDA receptor activation is probably not involved in the pathogenesis of motoneuron loss in the wobbler mouse.

Four children with Landau-Kleffner syndrome were studied over a six year period. They presented with acquired aphasia, epilepsy, and focal or generalized EEG discharges which were exacerbated during sleep. In addition, cerebral angiography demonstrated isolated arteritis of some branches of the carotid arteries in all cases. Computed tomographic and magnetic resonance images were normal. Nicardipine in a dose of 1 to 2 mg/kg/day, added to conventional anticonvulsant drugs provided effective supplementary control of seizures, of paroxysmal EEG discharges, and of language and behavioural disturbances, even several years after the onset of the disorder and in patients whose response to other medications, including steroids, had been poor. Interruption of nicardipine administration was followed by relapse of the language disorder. Repeat angiography was performed in all four patients and showed recanal-ization of obstructed vessels in two cases. Focal cerebral vasculitis may be the pathogenesis of the Landau-Kleffner syndrome and calcium channel blockers such as nicardipine may be effective and specific therapy.

Discontinuous non-circumferential lesions of tunica media were observed in four cases of traumatic rupture of the vertebral artery. We hypothesize that these lesions were due to mechanical disruption of smooth muscle cells and the liberation of catabolic enzymes with subsequent degradation of the arterial media. To test this hypothesis, healthy vertebral arteries were incubated with crude extracts of bovine smooth muscle cytosol in attempt to reproduce the histological changes of the arterial media in traumatized vertebral arteries. We observed cytosol-induced degradation of tunica media, characterized by pallor of staining with the Masson’s Trichrome method, which was due to catabolic enzyme activity that was effectively inhibited by heat inactivation of the cytosol. The cytosol-induced tinctorial changes were similar to the lesions of the tunica media in naturally-occurring cases of traumatic vertebral artery rupture. We conclude that although vertebral arteries can be ruptured by physical distortion alone, associated lesions of the tunica media are due to in situ trauma-associated release of heat-labile catabolic enzymes.

We report the first comparison of Chewable and Regular Carbamazepine (CBZ) tablets in children with epilepsy. Forty-four children receiving chronic monotherapy CBZ participated. In month 1 children received regular CBZ; in month 2, the same dose of Chewable CBZ. Once per week fasting predose CBZ and CBZ epoxide serum levels were determined. In a subset of 15 children, at the end of each month serum levels were obtained every 2 hours for 12 hours beginning pre-dose. Standards for CBZ and CBZ epoxide were tested in each centre. Overall, weekly levels showed no consistent differences between the month on chewable CBZ and regular CBZ. Seizure control and rates of reported side effects were similar. In five patients chewable CBZ produced higher peak CBZ levels while five had higher peaks with regular CBZ. In conclusion, regular and chewable CBZ often have unpredictable differences in peak but not trough levels of CBZ suggesting that peak level side effects with one form of CBZ might be alleviated by changing to the other.

We propose a new approach to staging the disease based on clinical and immunological response to treatment. We oppose clinical remission to immunological remission and define total clinical remission as the goal of therapy. We describe the use, side effects and indications of established therapies. Acetycholine esterase inhibitors are only a symptomatic treatment as is plasma exchange. Usefulness and limits of thymectomy, corticosteroids and immunosuppressants are described here. Their goal is to reduce the auto-immune process. Long-term hazards from these medications are described and methods to reduce their potential risks are suggested. We suggest the number of patients having life threatening complications while undergoing aggressive immunosuppression can be reduced by a systematic approach to follow-up. In the second part of this review article, adapting management to specific situations is emphasized in refractory disease, respiratory failure, neonatal and juvenile forms of the disease. The special situation of seronegative myasthenia is discussed.

Deprenyl is a synthetic, selective inhibitor of the monoamine oxidase-B enzyme system. The mechanism of its beneficial effect in early and advanced Parkinson’s disease is not settled. Increased striatal dopamine accumulation, sensitization of surviving dopamine neurons with increased dopamine production and reduced nigro-striatal toxicity may all contribute. The standard daily dose of deprenyl is 10 mg. Selectivity may be lost at higher doses. Deprenyl is especially indicated in untreated patients, improving up to 50 percent of patients with mild motor fluctuations. Major symptomatic benefit also occurs in occasional levodopa treated patients. Adverse effects are common, however. Increase dyskinesias, confusion and hallucinations, nausea and postural hypotension may necessitate drug withdrawal or the use of low dose regimens. Caution should be exercised with older patients, those with ulcer disease, which may be worsened by deprenyl, and individuals with active ischemic heart disease where the safety of this drug is not yet clear.

Many diseases with an auto-immune etiology have a skewed sex distribution. In the majority of instances, women are affected more frequently than men. A review of population studies demonstrates that the preponderance of women in multiple sclerosis (MS) is almost constant. We show that this preponderance is further increased in early as well as in late-onset cases, in familial cases as well as in MS twin pairs and that the HLA-DR2 allele, which has been associated with MS in Caucasian populations, is significantly more frequent in women than in men with MS. “Rules” have been established for multifactorial diseases; MS contravenes most of those rules. The skewed sex distribution in MS could be attributed to the known hormonal and gender influences on the immune response, as well as to genetic influences.