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Ballistic elbow flexion movements in patients with amyotrophic lateral sclerosis.

Patients with amyotrophic lateral sclerosis made stereotyped 20 degrees elbow flexion movements as rapidly as possible while surface EMG was recorded from biceps and triceps. The characteristic ballistic movement EMG pattern could be recognised in almost all the patients. The first agonist burst and the first antagonist burst, which are normally limited in duration, were prolonged in patients with clinical signs of pyramidal tract disease or alpha motor neurone disease or both. Prolongation of these components permits the muscles to generate sufficient forces to accomplish the movements.

Adult↗

Dementia paralytica: deterioration from communicating hydrocephalus.

Five patients suffering from dementia paralytica who failed to improve or deteriorated after one or several high dosage courses of penicillin, had pneumoencephalographic patterns suggesting communicating hydrocephalus. Measurements of the ventricular index, ratio of cella media to width of the temporal horn, and the callosal angle differed from that in seven cases of dementia paralytica with associated cerebral atrophy. An isotope cisternogram in three cases with communicating hydrocephalus further confirmed a blockage of the cerebrospinal fluid (CSF) at the parasagittal subarachnoid space. Three patients exhibited the full syndrome of gait apraxia, incontinence, and pyramidal tract signs associated with a severe degree of dementia. Shunting of the CSF in three cases was followed by immediate improvement in two, one in a longlasting way. No active parenchymal inflammation was observed in any of three brain biopsy samples taken during surgery, except for leptomeningeal fibrosis in one. Chronic leptomeningitis in dementia paralytica may impair subarachnoid CSF absorption with subsequent communicating hydrocephalus. Progression or inadequate responses after therapeutic dose of penicillin in dementia paralytica should prompt investigation for this complication as an alternative, effective treatment could be offered.

Adult↗

CNS involvement in malignant atrophic papulosis (Kohlmeier-Degos disease): vasculopathy and coagulopathy.

The clinical features in a 42 year old man with malignant atrophic papulosis with CNS involvement are described. They included mental dysfunction, paraesthesiae, weakness of left limbs, with pyramidal tract signs, bilateral ptosis, progressing to total ophthalmoplegia and obtundation. There were two crops of characteristic papular lesions on trunk and limbs, with terminal evidence of a coagulopathy and bruises, resulting in death in six months. Papular biopsy revealed multiple microinfarcts in the dermal collagen. The brain showed multiple small haemorrhagic infarcts of both hemispheres, the lower mid-brain, pons and a cerebellar peduncle. Microscopy showed fibrin exudation in the leptomeninges, various stages of thrombosis of small arteries without inflammatory reaction, and corresponding acute and subacute microinfarcts. The pathogenetic basis of the disease appeared to be a combined vasculopathy and coagulopathy.

Adult↗

Tri-cresyl phosphate neuropathy in Sri Lanka: a clinical and neurophysiological study with a three year follow up.

Clinical and neurophysiological findings in twenty patients intoxicated with tri-cresyl phosphate following consumption of contaminated gingili oil are reported. Marked distal axonopathy, high incidence of pyramidal tract dysfunction and minimal sensory abnormalities were the cardinal features. Despite pronounced motor weakness in the early stages, the patients showed remarkable improvement during a three year follow up.

Adolescent↗

Ataxia and other data reviewed in Charcot-Marie-Tooth and Refsum's disease.

The author reports his experience on Refsum's disease and that gained after personally examining in detail 64 patients with Charcot-Marie-Tooth disease over the past ten years. The "cerebellar" inco-ordination in Charcot-Marie-Tooth disease (with or without distal wasting) and in Refsum's disease is analysed. Some variations in the motor and sensory neuropathy of Charcot-Marie-Tooth disease and Refsum's disease are discussed. The adequacy of motor conduction velocity in genetically distinguishing types of the above mentioned familial peripheral neuropathies is reviewed. Data on the neuropathy assessed by modern techniques of three original patients of Roussy and Levy (1926) are given. The possibility of extensor plantar responses in patients with Charcot-Marie-Tooth and Refsum's disease without structural lesion of the pyramidal tract is pointed out. The existence of the association between Friedreich's ataxia and Charcot-Marie-Tooth disease is criticised. It is emphasised that spinocerebellar degeneration (other than Friedreich's ataxia) presenting with distal limb weakness and wasting and sensory impairment may mimic Charcot-Marie-Tooth disease.

Adolescent↗

Giant axonal neuropathy: observations on a further patient.

A further child with giant axonal neuropathy (GAN), abnormally curly hair and consanguineous parents is described. Of the 19 patients with GAN so far reported in the literature, six, including the present patient, have resulted from consanguineous marriages. This makes autosomal recessive inheritance of GAN highly probable. Our patient also exhibited cerebellar ataxia and signs of pyramidal tract damage; magnetic resonance brain imaging demonstrated abnormalities within the cerebellar and cerebral white matter. Myelinated nerve fibre density in the sural nerve was reduced to 6790/mm2 at age 8 years and had fallen to 3812/mm2 16 months later, indicating that progressive axonal loss occurs in GAN.

Axons↗

Lower motor neuron degeneration and familial predisposition to colonic neoplasia in two adult siblings.

A previously unreported association between a familial predisposition to colonic neoplasia and familial adult onset lower motor neuron (LMN) degeneration is reported. Two brothers presented at the ages of 53 and 44 years with multiple colonic adenomata and invasive colonic carcinoma respectively. Subsequently both developed a virtually identical pattern of motor neuron disease of progressive muscular atrophy type. At presentation both had LMN weakness affecting predominantly the upper limb and neck muscles. The disease progressed rapidly to involve the lower limb and bulbar musculature and both brothers died after a 15 month course. Necropsy was performed on one brother and showed pathological changes confined to the LMNs with no evidence of involvement of the pyramidal tracts or motor cortex. The combination of these diseases in two brothers may be of importance in the search for genes responsible for familial motor neuron disorders. It is suggested that a genomic search should be directed initially to the vicinity of known colon neoplasia genes, particularly 5q, 17q and 18q.

Adenocarcinoma↗

Transcranial magnetic stimulation in pontine infarction: correlation to degree of paresis.

Transcranial magnetic stimulation was performed in 20 patients with pontine infarction who had initially some degree of hemiparesis. Only patients with a well defined lesion on magnetic resonance imaging that was appropriate for the neurological signs were included. Recordings were made from the abductor pollicis brevis muscle (APB) bilaterally. The degree of hand paresis was estimated clinically and related to the following parameters: central motor conduction time (CMCT), interside latency difference of total latency, and amplitude ratio of affected to unaffected side. Increasing degree of paresis was associated with increasing latency parameters and decreasing amplitude ratio. In the four patients with severe paresis a low amplitude response could be evoked and CMCT was delayed by up to 10 ms. When the paresis had resolved at the time of transcranial magnetic stimulation CMCT was normal. However, amplitude ratio was less than 100% in all but one patient, with most of the values ranging between 40% and 60%, which indicates a subclinical pyramidal tract lesion. Median nerve sensory evoked potentials (SEP) and related interside latency difference to amplitude ratio N20/P25 were also recorded. In contrast to TCMS, decreased amplitude ratio of SEP was not associated with delayed latency. Clinically, the mild degree of and good recovery from paresis in ventral pontine infarction was remarkable.

Adult↗

Somatosensory and brainstem auditory evoked potential in congenital craniovertebral anomaly; effect of surgical management.

Clinical features and evoked potential recordings were analysed in 32 patients with congenital atlantoaxial dislocation before and after surgery. Seven patients (group 1) had atlantoaxial dislocation, while 22 patients had associated basilar invagination (group 2). In both groups, pyramidal tract signs, posterior column signs, wasting of the upper limbs, and abnormality of somatosensory evoked potentials (SSEP) were similar. Conversely, lower cranial nerve involvement and abnormal brainstem auditory evoked potentials (BAEP) were significantly more in patients with basilar invagination (p less than 0.05). All seven patients in group 1 and 17 patients in group 2 were operated upon. Clinical and electrophysiological deterioration were significant in patients with basilar invagination (group 2), following posterior fixation compared with group 1. Among the patients in group 2, who clinically deteriorated following posterior fixation, seven had transoral excision of odontoid and six of them improved both clinically and electrophysiologically. Two patients in group 2 had odontoid excision before posterior fixation, and in both the evoked potentials improved postoperatively. In group 1 the patient's BAEP remained unaffected following posterior fixation, however, in group 2, eight patients over 53% showed improvement in brainstem function following posterior fixation. This study shows the value of evoked potentials in congenital atlantoaxial dislocation, and rationalizes the surgical procedure in these patients. In patients with basilar invagination, odontoid excision is the preferred first stage procedure.

Atlanto-Axial Joint↗

Folate deficiency in cerebrospinal fluid associated with a defect in folate binding protein in the central nervous system.

An adult male patient of Dutch ancestry has a slowly progressive neurological disease characterised by a cerebellar syndrome, distal spinal muscular atrophy, pyramidal tract dysfunction, and perceptive hearing loss. A severe folate deficiency state was found in CSF in combination with a normal serum and red cell folate state. Two unknown abnormal metabolites were present in CSF. The concentration of immunoreactive folate binding protein in CSF was unusually low, whereas the concentration of the protein measured with radioligand (3H-folate) binding was unusually high. The transfer of folate over the choroid plexus seems to be disturbed, potentially reflecting a defect in the choroid plexus folate binder.

Adolescent↗

Hyperekplexia and trismus due to brainstem encephalopathy.

The brainstem is said to be the generator of pathological startle responses due to reticular reflex myoclonus or hyperekplexia. A patient with facial weakness, nystagmus, and pyramidal tract signs had generalised reflex spasms in response to auditory, visual and tactile stimuli which clinically and neurophysiologically resembled hyperekplexia. The case is unusual because as well as hyperekplexia, the patient's initial presentation was with an equally rare manifestation of brainstem pathology-brainstem mediated trismus. The causes of brainstem trismus and exaggerated startle responses are discussed with respect to their underlying mechanisms.

Brain Diseases↗

Atypical form of amyotrophic lateral sclerosis.

OBJECTIVE: To investigate patients with an unusual type of muscular atrophy confined to the upper limbs (proximally dominant) and the shoulder girdle, while sparing the face and the legs until the terminal stage. METHODS: Eight patients (six men and two women) were clinically examined. The age at onset ranged from 42 to 73 years, and the clinical course varied from 28 to 81 months. There was no family history of motor neuron disease in any of these patients. Necropsy was performed in two of them. RESULTS: All eight patients basically showed a similar distribution of muscular weakness and atrophy. Subluxation of the shoulder joints was found in all patients. Reflexes were absent in the upper limbs in all patients, but were almost normal in the face and legs in most patients. Pathological reflexes could be elicited in only one patient. Electromyography showed typical neurogenic changes in the limbs of all patients. Cervical MRI disclosed moderate spondylotic changes in seven patients. Antiganglioside antibodies were negative in six patients tested. Abnormal trinucleotide (CAG) repeat expansion of androgen receptor gene was not recognised in five patients examined. Bulbar involvement developed in three patients during the course of the disease. At necropsy, one patient showed degeneration of the pyramidal tracts and motor cortex including Betz cells as well as loss of spinal anterior horn cells and brainstem motor neurons, which is consistent with ALS; in another patient there was neuronal loss of anterior horn cells at the spinal cord accompanied by astrogliosis, whereas the motor cortex and brainstem motor nuclei were relatively well preserved. Intracytoplasmic inclusions such as Bunina bodies, skein-like inclusions, and Lewy body-like inclusions were found in both patients. CONCLUSION: These patients with their peculiar pattern of muscular atrophy seem to have ALS or a subtype of ALS.

Adult↗

Combined functional magnetic resonance imaging and diffusion tensor imaging demonstrate widespread modified organisation in malformation of cortical development.

A patient with a mild left hemiparesis and a malformation of cortical development in the right hemisphere was investigated with fMRI (functional magnetic resonance imaging) and DTI (diffusion tensor imaging). The motor cortex was studied using a finger tapping fMRI experiment. The fibre orientation was studied by displaying the principal eigenvector of the diffusion tensor in the spatially normalised brain of the patient and of control subjects. In addition, the anisotropy (directionality) of water diffusion of the patient was statistically compared with control subjects. The malformation was located in the right central region in the expected position of the motor cortex. fMRI showed activation anterior and posterior to the malformation. DTI disclosed that fibres with rostrocaudal orientation, presumably representing the pyramidal tract, were deviating from their normal orientation and passing around the malformation. There were widespread regions of reduced anisotropy affecting both hemispheres. In conclusion, fMRI and DTI provided concordant information showing widespread modified functional and structural organisation including regions which appeared normal on standard imaging.

Adult↗

Homozygous deletion mutation of the parkin gene in patients with atypical parkinsonism.

Autosomal recessive juvenile parkinsonism (AR-JP) is characterised by homogenous clinical features and selective degeneration of nigral neurons. Recent progress in molecular genetic analyses of AR-JP has led to the identification of a novel ubiquitin-like protein, parkin, whose precise function still remains to be elucidated. Two unrelated Japanese families had levodopa unresponsive parkinsonism complicated with cerebellar and pyramidal tract dysfunction. Genetic analysis of the parkin gene and mRNA in both families disclosed identical mutations with large deletions extending from exons 3 to 4. These results suggest that the parkin protein possesses an important function not only in the substantia nigra but also in extranigral neurons of the CNS and that the phenotype of multiple system dysfunction can also be a complication in patients with AR-JP due to variations in sites of or changes in functions by parkin mutation.

Blotting, Southern↗

Peripheral and segmental spinal abnormalities of median and ulnar somatosensory evoked potentials in Hirayama's disease.

OBJECTIVES: To investigate the origin of juvenile muscle atrophy of the upper limbs (Hirayama's disease, a type of cervical myelopathy of unknown origin). SUBJECTS: Eight male patients were studied; data from 10 normal men were used as control. METHODS: Median and ulnar nerve somatosensory evoked potentials (SEP) were recorded. Brachial plexus potentials at Erb's point (EP), dorsal horn responses (N13), and subcortical (P14) and cortical potentials (N20) were evaluated. Tibial nerve SEP and motor evoked potentials (MEP) were also recorded from scalp and spinal sites to assess posterior column and pyramidal tract conduction, respectively. RESULTS: The most important SEP findings were: a very substantial attenuation of both the EP potentials and the N13 spinal responses; normal amplitude of the scalp N20; and normal latency of the individual peaks (EP-N9-N13-P14-N20). Although both nerves were involved, abnormalities in response to median nerve stimulation were more significant than those in response to ulnar nerve stimulation. There was little correlation between the degree of alterations observed and the clinical state. Latencies of both spinal and cortical potentials were normal following tibial nerve stimulation. The mean latency of cervical MEP and the central conduction time from the thenar eminence were slightly but significantly longer in patients than in controls. CONCLUSIONS: The findings support the hypothesis that this disease, which is clinically defined as a focal spinal muscle atrophy of the upper limb, may also involve the sensory system; if traumatic injury caused by stretching plays a role in the pathogenesis, the damage cannot be confined to the anterior horn of the spinal cord.

Adolescent↗

A case-control study of motor neurone disease: its relation to heritability, and occupational exposures, particularly to solvents.

Motor neurone disease (MND) was studied in relation to various determinants in a case-control study covering nine counties in southern Sweden. A questionnaire about occupational exposures, medical history, lifestyle factors etc was given to all cases in the age range 45-79 and to a random sample of 500 population controls in the same age range. The questionnaires were answered by 92 cases and 372 controls, a response rate of 85% and 75% respectively. Among men high Mantel-Haenszel odds ratios (MHORs) were obtained for electricity work (MHOR = 6.7, 95% confidence interval (95% CI) 1.0-32.1), welding (MHOR = 3.7, 95% CI 1.1-13.0), and impregnating agents (MHOR = 3.5, 95% CI 0.9-13.1). Heritability with regard to a neurodegenerative disease or thyroid disease seemed to predispose to a risk of developing MND (OR = 2.1, 95% CI 1.0-4.3). The highest OR was found for the combination of such heritability, exposure to solvents, and male sex (OR = 15.6, 95% CI 2.8-87.0), a combination that occurred for seven cases and three controls. Hereditary factors and external exposures had a different distribution among cases with the spinal type of MND than among cases with involvement of the pyramidal tract or bulbar paresis also.

Age Factors↗

Ionic changes induced by excitatory amino acids in the rat cerebral cortex.

The ionic mechanisms underlying the action of excitatory amino acids were investigated in the rat motor cortex. Ion-selective microelectrodes were attached to micropipettes such that their tips were very close and local changes in extracellular concentration of sodium, calcium, and potassium ions elicited through ionophoretic applications of glutamate (Glu) and of its agonists N-methyl-D-aspartate (NMDA), quisqualate (Quis), and kainate (Ka) were measured. These agents produced moderate increases in [K+]o (up to 13 mM) but, in contrast, substantial tetrodotoxin-insensitive decreases in [Na+]o (maximally of 60 mM). NMDA-induced sodium responses could be blocked by manganese, while the Quis- and Ka-induced responses were not. Quis and Ka produced increases in [Ca2+]o or biphasic responses while NMDA, even with small doses, induced each time drastic decreases in [Ca2+]o (maximally of 1.15 mM), which could be attenuated or blocked by manganese but not by organic calcium channel blockers. NMDA responses could be abolished by reduced doses of 2-amino-phosphonovalerate. The largest Glu- and NMDA-induced calcium responses were observed in the superficial cortical layers, but such maxima disappeared after selective degeneration of pyramidal tract neurons. All amino acids produced sizeable reductions in the extracellular space volume. The following can be concluded. (i) All the excitatory amino acids tested induce an increased permeability to sodium and potassium ions. (ii) In addition, the NMDA-operated channels have specifically a large permeability for calcium, although calcium ions contribute only by less than 10% to the NMDA-induced inward currents.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Spatial coding of visually guided arm movements in primate motor cortex.

Previous studies of the motor cortex in behaving animals were focused on the relations between the activity of single cells, usually pyramidal tract neurons, and parameters of isometric contraction (e.g., intensity of force) or parameters of movement along one axis (e.g., flexion-extension) of a single joint (e.g., elbow or wrist). However, the commonly meaningful behavioral parameter is the trajectory of the hand in extrapersonal space, which is realized by simultaneous motions about two or three joints (e.g., elbow, shoulder, wrist) and concurrent engagement of several muscles. The spatial parameters of a straight trajectory are its direction and extent. We hypothesized that a major function of the motor cortex, among other possible roles, is the specification and control of the direction of the movement trajectory in space. This reference of motor cortical function to the control of spatial aspects of the trajectory differentiated our approach from the other approaches outlined above. We investigated the directional selectivity cells in the arm area of the motor cortex by recording their activity while monkeys moved their hands in various directions in space towards visual targets. There were two salient findings of these studies. First, the intensity of the discharge of single cells varies in an orderly fashion with the direction of movement in space, so that the discharge rate is highest with movements in a preferred direction, and decreases progressively with movements made in directions more and more away from the preferred one. Thus single cells are broadly tuned around a preferred direction which differs among different cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗