There is debate on the neurological impact of chronic exposure to Manganese (MN).

MN burden from rural well water was studied cross-sectionally in two proband cohorts from rural dwellings located in northern Germany. Both cohorts had exposure times for up to 40 years and were separated on the basis of well water MN content. Group A (41 subjects; mean age 57.5 years) was exposed to MN water contents of at least 0.300 mg/l (range 0.300 to 2.160), while group B (74 subjects; mean age 56.9 years) was exposed to concentrations of less than 0.050 mg/1. Both proband groups were homogenous with regard to age, sex, nutritional habits, and drug intake. Neurological assessments by clinical investigators blinded for proband’s exposure status was done using structured questionnaires, standardized neurological examination with assessment of possible Parkinsonian signs by the Columbia University Rating Scale, and instrumental tests of fine motor coordination.

No significant difference in any neurological measure was found between groups. Results were not confounded by demographic and dietary features.

Exposure to high body burden of MN does not result in detectable neurological impairment. Exposure to MN in drinking water does not seem to be a risk factor for idiopathic Parkinson’s disease.

Stimulation of the central cholinergic system results in generalized epileptic seizures. The goal of this study was to map the epileptogenic effects of the cholinergic agonist, carbachol injected into different sites of the basal forebrain and diencephalon of the rat brain.

Carbachol was injected directly into the brain in a dose of 1 or 3 (jg. Seizures were assessed behaviourally on a five-stage scale with electroencephalographic controls. Seizures at stage 1 were the least severe and those at stage 5 the most severe.

Injections of high dose carbachol (3 (jg) induced seizures from 40% of all injected brain sites. Injections of low dose carbachol (1 ug) or isotonic saline into the same brain sites did not cause any behavioural or electrographic seizures. The majority of sites (84%) producing generalized seizures (stage 5) were concentrated in or around the zona incerta.

Within the anatomical limits of the study, the zona incerta is the area most sensitive to carbachol-induced generalized seizures.

As in the brain, recent evidence has suggested a defect in the microcirculation during the reperfusion period after spinal cord ischemia. This investigation was undertaken in order to delineate blood flow dynamics in the postischemic spinal cord of the rat.

Male Sprague-Dawley rats underwent cross-clamping of the aorta and subclavian arteries (XC) for 11 minutes. Spinal cord blood flow (SCBF) was measured by autoradiography in the gray and white matter of cervical (Ce), thoracic (Th) and lumbar (Lu) regions during XC, 1 h, 6 h and 24 h (XC n = 8, 1 h n = 9, 6 h n = 9, and 24 h n = 11, groups) after XC. Control groups underwent surgical manipulations and SCBF measurement but no XC (Sham 1, n = 8), or clamping of the subclavian arteries only (Sham 2, n = 8).

In Ce cord, there was no difference between SCBF of 1 h, 6 h, 24 h and Sham 1. In Th cord, SCBF was reduced during XC (P < 0.003 vs. Sham 2), 1 h, 6 h (P < 0.04 and P < 0.01 vs. Sham 1). In Lu cord, SCBF was not detectable in XC, and depressed in 1 h (P < 0.003) and 6 h (P < 0.003). There was no difference between 24 h and Sham 1 in Ce, Th, and Lu cords.

The study demonstrated a period of delayed postischemic hypoperfusion in the white and gray matter of Th and Lu cord segments lasting 6 h after XC. The phenomenon may play an important role in the ultimate fate of neural elements with borderline viability after ischemic injury.

Genetic factors may be important in the etiology of subarachnoid hemorrhage (SAH) and intracranial aneurysm (IA) formation. Several studies have reported the familial occurrence of SAH and IA, although in most cases asymptomatic family members were not studied with elective angiography. The examination of data from large sibships could provide important information about the frequency of IA occurrence in at-risk individuals and the mode of inheritance for familial SAH/1A.

We reviewed published case series of sibships with SAH and at least four siblings, in which at least one sibling underwent elective angiography. Data were collected on age-of-onset, clinical events, presence of hypertension, angiographic findings, and outcome. Patients were classified as “affected” if they had a SAH or if an IA was detected by elective angiography, and “unaffected” if they were asymptomatic and had a negative angiogram.

Seven case series with 52 individuals (26 men and 26 women) met our inclusion criteria. The sibships ranged from 6 to 13 members. Most of the siblings (32 of 52, 61%) were asymptomatic, 18 (35%) had a SAH, and 2 (4%) had focal symptoms but no SAH. Elective angiography of 34 siblings showed an IA in 11 (32%) and was negative in 23 (68%). The overall rate of affecteds (SAH or IA) was 56%.

Based on data from these sibships, angiography of asymptomatic at-risk siblings demonstrated an IA in almost one-third of cases. Familial SAH/IA segregated with a pattern that was consistent with an autosomal dominant trait in this selected series of sibships, although other factors could produce these findings.

To investigate the effects of aging and anoxia on the nucleus accumbens.

The number of neurons in nucleus accumbens and caudate neucleus in 35 patients over 65 and 35 under 65 years, all without neurological or psychiatric diseases were counted.

There was no statistically significant difference between the number of neurons in the accumbens in the two groups, but there was a decrease in the number of neurons in the elderly group. There was no reduction in volume of the neuronal nucleoli of the accumbens measured in 12 elderly patients compared to controls. These data suggest a sparing of the accumbens from changes associated with aging. There was relative preservation of the nucleus accumbens in 3 patients with anoxic encephalopathy.

These results show that accumbens was resistant to both aging and anoxia, the mechanism of which is discussed.

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.

Severe spasticity unresponsive to oral drugs may respond satisfactorily to baclofen delivered intrathecally.

Intrathecal baclofen (IB) therapy delivered by means of implanted infusion pumps was used for nine patients with severe spasticity. Six patients had multiple sclerosis, two cervical spinal cord injury, and one head injury. All were non-ambulatory.

Patients showed improvement in many areas, including ability to transfer, seating, pain control, personal care, and liability to skin breakdown. Before IB therapy, only three of the nine patients were able to live at home in the community and six were institutionalized. At the end of our follow-up period, only one patient remained institutionalized, three lived in group homes and five lived at home in the community. In the year preceding pump implantation, the nine patients spent a total of 755 days in acute care hospitals. In the year following onset of IB therapy, they spent only 259 days in hospital.

IB therapy can improve patient quality of life and can be cost-effective in carefully selected patients with severe spasticity and disability. The drug delivery catheter is that part of the therapeutic system most vulnerable to failure. Because of the varied expertise required to manage these patients effectively, and the potential for a variety of complications, it is essential that an IB program is supported by a well-organized multi-disciplinary medical team.

Postural instability is a common problem in patients with Parkinson’s disease. This paper reports results of a study undertaken to investigate some of the possible mechanisms responsible for this instability.

Preparatory postural adjustments associated with a lateral leg raising task were studied in five parkinsonian patients and four age-matched controls. Recordings included ground reaction forces, kinematics, and surgace EMG activity from multiple leg muscles.

In normal subjects there was a well-defined sequence of events preceding the onset of leg elevation, beginning with a transfer of centre of foot pressure (CP), initially toward the moving leg and then back to the support side, followed by displacement of the trunk toward the support side. In the more severely affected parkinsonian patients, the amplitude of the the initial displacement of CP was markedly reduced. The interval between the earliest force changes and the onset of leg elevation was prolonged and the relative timing of the kenematic adjustments during this interval was disrupted. In addition the alternating burst and periods of inhibition observed in the EMG recordings from the normal subjects were replaced by continuous tonic EMG activity.

These observations suggest that abnormalities in programming preparatory postural adjustments may contribute to postural instability in some patients with advanced Parkinson’s disease.

We tested the effect of thiopental on the excitability of the corticospinal-motoneuron axis in normal human subjects.

Magnetic stimulation was used to excite the neurons in the motor cortex which give rise to the fast conducting corticospinal pathway. The characteristics of the composite excitatory post-synaptic potentials (EPSPs) produced in individual spinal motoneurons by cortical stimulation were derived from changes in the firing probability of voluntarily activated motor units of the first dorsal interosseous muscle.

In 5 normal subjects, we found that thiopental, in incremental doses sufficient to sustain drowsiness (total dose 75 to 175 mg), significantly reduced the amplitude of these composite EPSPs.

Thiopental reduced the facilitation of motoneurons from the cortex most likely by depressing cortical neurons.

In order to explain the mechanism for the sparing of the nucleus accumbens in several pathologic conditions, the accumbens, caudate and putamen were examined in an experimental model.

The neurons in these regions from twenty adult rats were stained for the enzyme nicotinamide adenine dinucleotide phosphate (NADPH-diaphorase) and quantified.

Positive neurons in the nucleus accumbens were more abundant than in the caudate and putamen.

Since these neurons have been shown to be resistant to ischemia and degeneration, it is suggested that the mechanism for the sparing of the nucleus accumbens is related to the presence of a large number of NADPH-diaphorase positive neurons.

One of the major symptoms of postpoliomyelitis syndrome (PPS) is disabling generalized fatigue. Subjects with PPS also report muscle fatiguability and display electrophysiologic evidence of anticholinesterase-responsive neuromuscular junction transmission defects, suggesting that anticholinesterase therapy may be useful in the management of disabling fatigue.

We initiated an open trial of the oral anticholinesterase pyridostigmine, up to 180 mg per day, in 27 PPS patients with generalized fatigue and muscle fatiguability. Response to pyridostigmine was assessed with the Hare fatigue scale, the modified Barthel index for activities of daily living, and a modified Klingman mobility index.

Two patients could not tolerate the medication. After one month of therapy, 16 patients (64%) reported a reduction in fatigue on the Hare fatigue scale; three of 16 showed improvement on the modified Barthel index for activities of daily living, and two of 16 experienced improvement on a modified Klingman mobility index. Pyridostigmine responders were significantly more fatigued than non-responders on the pre-treatment Hare score, but were not significantly different with regard to age, sex, age at acute poliomyelitis, or severity of acute poliomyelitis.

Pyridostigmine may be useful in the management of fatigue in selected patients with PPS. Response to pyridostigmine may be predicted by severity of pre-treatment fatigue.

To review the clinical characteristics and associated features found in patients with psychogenic dystonia.

A 10 year retrospective chart review of all patients diagnosed by the author as having psychogenic dystonia.

Eighteen patients fulfilled diagnostic criteria for “Documented” or “Clinically Established” psychogenic dystonia. Clinical characteristics of the dystonia were inconsistent or incongruous with established forms of organic dystonia. Fourteen of the 18 patients had a known precipitant. In most, the onset was abrupt and progression occurred rapidly, often to fixed dystonic postures. In contrast to idiopathic dystonia, involvement of the legs was common (12 patients), despite onset in adult life. Although cases of isolated paroxysmal dystonia were excluded in the review, 10 patients had paroxysmal worsening of dystonia or other abnormal movements. Pain was a prominent feature in 14 of 16 patients with the complaint and 1 patient with documented psychogenic dystonia also had well established reflex sympathetic dystrophy (RSD). Other psychogenic movement disorders, psychogenic neurological signs and multiple somatizations were common. Long-term follow up was available for less than one-half of the patients. Outcome varied considerably; some patients had complete resolution of symptoms (including 1 who had undergone 2 previous thalamotomies) and others remained disabled by persistent dystonia.

Dystonia is uncommonly due to primary psychological factors. At times this is an extremely difficult diagnosis to make and even when the diagnosis is confirmed, management remains very challenging. Future studies are required in hopes of providing more efficient means of distinguishing psychogenic dystonia from other dystonic syndromes especially those which rarely follow peripheral injury or accompany RSD/causalgia syndromes.

To assess the reliability of interictal spike discharge in routine electroencephalography (EEG) testing in children.

EEG results of all children diagnosed in Nova Scotia with epilepsy onset between 1977–85 (excluding myoclonic, akinetic-atonic and absence) were reviewed. The results of the EEG at time of diagnosis (EEG1) were compared with those of a second EEG (EEG2) within 6 months.

Of 504 children with epilepsy, 159 had both EEG1 and EEG2. EEG2 was more likely ordered if EEG1 was normal or showed focal slowing but less likely if EEG1 contained sleep (p < 0.05). EEG1 and EEG2 were both normal in 23%. If EEG1 was abnormal, there was a 40–70% discordance for the type of abnormality on EEG2. Abnormalities were present on both EEG1 and EEG2 in 67 cases. Of the 42/67 with major focal abnormalities on EEG1, 7 had only generalized spike wave on EEG2. Of the 17/67 with only generalized spike wave on EEG 1, 7 showed only major focal abnormalities on EEG2. Statistical testing showed low Kappa scores indicating low reliability.

The interictal EEG in childhood epilepsy appears to be an unstable test. A repeat EEG within 6 months of a first EEG may yield different and sometimes conflicting information.

In nine patients, suprascapular nerve palsy followed serious accidents associated with fractures of the cervical vertebrae, clavicle or scapula and after weight lifting, wrestling and a fall on the elbow or shoulder.

All patients were examined as to muscle wasting, weakness and shoulder fixation. EMG examination was done in all cases and six patients underwent surgical exploration.

The palsy was incomplete on clinical and EMG examination in all patients. On exploration, scarring, entrapment, tethering or kinking at the suprascapular notch was found in four and two had post-traumatic neuromas.

In contrast to published studies, none of our patients presented with shoulder pain, a spontaneous onset nor with involvement limited to the infraspinatus muscle. The differential diagnosis should include C5 root lesion, brachial plexus neuritis, frozen shoulder and tear of the rotator cuff.

Multiple Sclerosis (MS) is associated with a high risk of developing major depression, but depression in MS patients frequently goes undetected and untreated. The current study examined the clinical utility of the Beck Depression Inventory (BDI) as a screening measure for major depression in newly diagnosed MS patients.

Forty-six new referrals to an MS clinic completed the BDI and participated in a structured interview for major depression, within 2 months of the diagnosis of MS.

According to DSM-III-R criteria, 40% of patients were diagnosed with major depression, 22% had adjustment disorder with depressed mood, and 37% showed no evidence of mood disorder. Sensitivity and specificity values, and positive and negative predictive values are reported for every BDI cut-off score between 9 and 21.

A BDI cut-off score of 13 (sensitivity = .71, specificity = .79) is recommended as optimal for use in screening for major depression in newly diagnosed MS patients. The use of the BDI as a screening measure for major depression must proceed with caution given that a cut-off score of 13 still yielded a false-negative rate of 30%.