Showing papers in "Neurology in 1991"

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD): Part II. Standardization of the neuropathologic assessment of Alzheimer's disease

Abstract: The Neuropathology Task Force of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed a practical and standardized neuropathology protocol for the postmortem assessment of dementia and control subjects. The protocol provides neuropathologic definitions of such terms as "definite Alzheimer's disease" (AD), "probable AD," "possible AD," and "normal brain" to indicate levels of diagnostic certainty, reduce subjective interpretation, and assure common language. To pretest the protocol, neuropathologists from 15 participating centers entered information on autopsy brains from 142 demented patients clinically diagnosed as probable AD and on eight nondemented patients. Eighty-four percent of the dementia cases fulfilled CERAD neuropathologic criteria for definite AD. As increasingly large numbers of prospectively studied dementia and control subjects are autopsied, the CERAD neuropathology protocol will help to refine diagnostic criteria, assess overlapping pathology, and lead to a better understanding of early subclinical changes of AD and normal aging.

The International Classification of Sleep Disorders: Diagnostic and Coding Manual

Abstract: I congratulate the American Sleep Disorders Association for this outstanding manual, modeled after DSM-111 and consistent in style with the ICD-9-CM Classification. Like the DSM-111, it is more than an outline; it includes diagnostic criteria, clinical course, predisposing factors, prevalence, differential diagnosis, and a bibliography for each of the numerous disorders. The book obviously is essential for polysomnographers, but all neurologists seeing patients with sleep disorders or sleep-related phenomena should have i t available.

Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction

Abstract: Previous frequency estimates of cognitive dysfunction in multiple sclerosis have ranged from 54 to 65 percent. These studies may overestimate the frequency in the general MS population, since the patients in these studies were recruited from clinic populations. In the present study, we administered a comprehensive neuropsychological test battery to 100 community‐based MS patients and 100 demographically matched healthy controls. Of 31 cognitive test indices examined, 48 MS patients and five controls were impaired on four or more test indices, yielding an overall frequency rate of 43% for the MS group. The pattern of cognitive decline was not uniform: MS patients were more frequently impaired on measures of recent memory, sustained attention, verbal fluency, conceptual reasoning, and visuospatial perception, and less frequently impaired on measures of language and immediate and remote memory. We developed a brief (20‐minute) screening battery empirically by selecting the four most sensitive test indices from the comprehensive battery. The brief battery yielded a sensitivity value of 71% and a specificity value of 94% in discriminating cognitively intact from impaired MS patients, as defined by the comprehensive battery. Cognitive impairment was not significantly associated with illness duration, depression, disease course, or medication usage, but was significantly (albeit weakly) correlated with physical disability. NEUROLOGY 1991;41:685‐691

Cognitive dysfunction in multiple sclerosis. II. Impact on employment and social functioning

Abstract: We designed a study to assess the specific contribution of cognitive dysfunction to multiple sclerosis patients9 problems in daily living. Based on the results of a comprehensive neuropsychological test battery, we classified 100 MS patients as either cognitively intact (N = 52) or cognitively impaired (N = 48). In addition to a neurologic examination, MS patients completed questionnaires on mood and social functioning, underwent a comprehensive in‐home occupational therapy evaluation, and were rated by a close relative or friend regarding specific personality characteristics. While there were no significant differences between the two groups on measures of physical disability and illness duration, patients in the cognitively impaired group were less likely to be working, engaged in fewer social and avocational activities, reported more sexual dysfunction, experienced greater difficulty in performing routine household tasks, and exhibited more psychopathology than cognitively intact patients. These findings suggest that cognitive dysfunction is a major factor in determining the quality of life of patients with MS. NEUROLOGY 1991;41:692‐696

Mild cognitive impairment in the elderly: predictors of dementia.

Abstract: We conducted full diagnostic evaluations, including a comprehensive cognitive assessment battery, of a group of 32 elderly subjects with a clinically identified mild cognitive impairment and a group of 32 age-matched and education-matched normal subjects. The mildly impaired subjects performed significantly more poorly than the controls on tests of recent memory, remote memory, language function, concept formation, and visuospatial praxis. Follow-up evaluations of cognitive status 2 years later revealed clinically detectable cognitive decline relative baseline in 23 (72%) of the mildly impaired subjects. Several of the objective psychological tests accurately discriminated at baseline between the decliners and nondecliners in the mildly impaired group. Among the 20 mildly impaired subjects with no complicating conditions, 16 exhibited cognitive deterioration between baseline and follow-up. These results suggest that most elderly subjects with mild cognitive deficits, as determined by clinical evaluation and objective psychological testing, will manifest the progressive mental deterioration characteristic of dementia and that psychometric predictors can be used to distinguish between benign and more significant underlying disorders in mildly impaired elderly subjects.

Nomenclature and research case definitions for neurologic manifestations of human immunodeficiency virus-type 1 (HIV-1) infection

Abstract: Infection with human immunodeficiency virus-type 1 (HIV-1) has been associated with avariety of neurologic disorders thought to be caused, directly or indirectly, by HIV-1.1-6 Although these disorders have been described clinically, there is no consensus terminology or criteria for diagnosis. To develop consensus nomenclature and case definitions for HIV-1-associated neurologic conditions for research purposes, the American Academy of Neurology AIDS Task Force convened a working group of neurologists, neuropsychologists, psychiatrists, and sociologists that included representatives of the American Neurological Association, the World Federation of Neurology, the International Neuropsychological Society, the National Academy of Neuropsychology, the American Psychological Association, the American Psychiatric Association, the World Health Organization, and the Centers for Disease Control (CDC). These definitions have been developed in conjunction with the International Classification of Diseases-10 (ICD-10, unpublished draft of the World Health Organization) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV, unpublished draft of the American Psychiatric Association). Although consistent with the ICD-10, the definitions are not identical. HIV-2 may cause similar disorders, but the neurologic manifestations of HIV-2 are unknown and are not addressed in this article.

Prevalence of Alzheimer's disease and other dementias in an elderly urban population: relationship with age, sex, and education.

Abstract: We studied the prevalence of different types of dementia in an elderly population in Stockholm, Sweden, in relation to age, sex, and education. The study confirmed Alzheimer9s disease (AD) as the most frequent type of dementia and the positive association of dementias with age, even in the most advanced ages. In contrast to previously reported data, we found the same proportion of AD and vascular dementia in the different age strata, and no sex differences regarding the prevalence of different dementia types. Finally, less educated people had a higher prevalence of all dementias, due essentially to a higher prevalence of alcoholic dementia and unspecified type of dementia. The prevalence of AD was similar across different levels of education.

Induction of speech arrest and counting errors with rapid-rate transcranial magnetic stimulation.

Abstract: Six adult epileptic patients underwent rapid-rate transcranial magnetic stimulation (rTMS) at stimulation rates of up to 25 Hz with an 11-cm water-cooled round coil held flat on the scalp, centered over 15 different positions on each side of the scalp. The trains of stimuli were for 10 seconds while the patients counted aloud. rTMS centered over D5 or D7 induced reproducible speech arrest in all patients and counting errors in three when applied at lower intensities. There were no such speech disturbances by rTMS centered over the different positions on the right side. Intracarotid amobarbital test (IAT) demonstrated left hemispheric language dominance in all patients. Lateralization of speech arrest induced by rTMS correlated with the IAT results and may be helpful for noninvasive determination of hemispheric language dominance.

Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia

Abstract: We studied the analgesic efficacy of an intravenous infusion of lidocaine and morphine in 19 adults with well-established postherpetic neuralgia in a three-session, randomized, double-blind, placebo-controlled trial. Compared with saline placebo, both lidocaine and morphine reduced pain intensity. Reductions in pain did not correlate with side effects produced by the infusions. For morphine, there was a significant correlation between reductions in pain intensity and blood level achieved. In the majority of subjects who reported definite pain relief, allodynia also disappeared. The results show that neuropathic pain can respond to opioids and to systemically administered local anesthetic drugs.

Very mild Alzheimer's disease: Informant‐based clinical, psychometric, and pathologic distinction from normal aging

Abstract: We compare clinicopathologic data from 10 subjects identified in the very mild stage of senile dementia of the Alzheimer type with findings from similar studies in four cognitively normal subjects We based the diagnosis of very mild dementia in the 10 subjects on informant reports and the judgment of experienced clinicians Deficits of some psychometric measures of memory, language, and speeded psychomotor performance were observed for these subjects The histologic markers of Alzheimer's disease, including neurofibrillary tangles and both the "diffuse" and classic subtypes of senile plaques, were present in the neocortex in all 10 subjects but essentially were absent in the four controls These findings indicate that even "questionable" dementia can be diagnostic for Alzheimer's disease Furthermore, because truly normal aging may be unaccompanied by neocortical senile plaques and neurofibrillary tangles, the presence of these lesions should suggest the possibility of clinically undetected Alzheimer's disease

The risk of seizure recurrence following a first unprovoked seizure: A quantitative review

Abstract: Knowledge of the recurrence risk following a first unprovoked seizure and the predictors of that risk are necessary for rational treatment decisions. Published estimates of recurrence risk range from 23% to 71%. In a meta-analysis of 16 reports, three methodologic factors explained much of the reported variation: (1) study inclusion criteria, ie, whether patients were enrolled at the time of their first seizure or if patients with prior seizures were included; (2) retrospective versus prospective ascertainment of patients; (3) the interval between the first seizure and the time at which risk was assessed. The average recurrence risk across the 16 studies was 51%. The risk was 40% and 52% in prospective and retrospective studies that employed first-seizure methods and 67% in non-first seizure studies. At or near 2 years following the first seizure, the recurrence risk was 36% and 47% in prospective and retrospective first-seizure studies. The distribution of prognostic factors was also important. Seizure etiology and the EEG were the strongest predictors of recurrence distinguishing between patient subgroups, with recurrence risks as low as 24% and as high as 65%. Partial seizures were associated with an increased recurrence risk, but not consistently. There is considerable agreement among studies concerning the recurrence risk following a first seizure, and much of the discrepancies among studies can be explained by differences in study methods and distributions of important prognostic factors.

Quantification of magnetic resonance scans for hippocampal and parahippocampal atrophy in Alzheimer's disease.

Abstract: The brains of patients with Alzheimer's disease (AD) invariably exhibit neuropathology in the hippocampus and entorhinal cortex when examined postmortem. Magnetic resonance imaging (MRI) offers a noninvasive, high-resolution method for quantifying volumetric changes in the AD brain antemortem. Eight patients diagnosed with probable AD and 7 age-matched controls had MRI scans and were tested on a battery of cognitive and olfactory tests. The hippocampus and entorhinal cortex (parahippocampal gyrus) showed significant atrophy, with over 40% reduction in size. Areas of the brain that are not highly involved in the degenerative state of AD, such as the striatum, did not show significant volumetric changes. Hippocampal and parahippocampal gyrus volumes had the highest correlation with scores on the Mini-Mental State Examination (r = 0.89), with lower correlations for a smell identification test (r = 0.65), odor match-to-sample test (r = 0.72), and a visual match-to-sample test (r = 0.26).

Symptoms and disease associations in idiopathic intracranial hypertension (pseudotumor cerebri) A case‐control study

Abstract: To identify the symptoms and coexisting medical conditions associated with idiopathic intracranial hypertension (IIH), we administered an 83-item questionnaire at the time of diagnosis to 50 IIH patients and 100 aged-matched controls. Ninety percent of the IIH patients were women; the mean age was 33. Obesity and recent weight gain were much more common among patients than controls. Symptoms most commonly reported by IIH patients were headache (94%), transient visual obscurations (TVO) (68%), and intracranial noises (ICN) (58%). Daily occurrence of these symptoms was much more common among patients than controls. Controls also reported these and other IIH symptoms, but at lower frequencies. Several conditions previously associated with IIH were no more common in patients than controls including iron deficiency anemia, thyroid disease, pregnancy, antibiotic intake, and use of oral contraceptives. We conclude that previous studies of IIH, mostly uncontrolled and retrospective, have underestimated the frequency of symptoms in IIH patients and reported chance and spurious associations with common medical conditions and medications. The profile of a young obese woman with headaches and either TVO or ICN should alert the clinician to the diagnosis of IIH, especially when the symptoms occur daily.

Cause of death in patients attending multiple sclerosis clinics.

Abstract: Between 1972 and 1988, 145 deaths occurred among 3,126 patients attending the Multiple Sclerosis (MS) Clinics in Vancouver, British Columbia (N = 1,583), and London, Ontario (N = 1,543). We could determine the exact cause of death in 82.1% of cases (119 of 145). Of the 119 patients for whom the cause of death was known, 56 deaths (47.1%) were directly attributed to complications of MS. Of the remaining 63 deaths, 18 (28.6%) were suicides, 19 (30.2%) were due to malignancy, 13 (20.6%) to an acute myocardial infarction, seven (11.1%) to stroke, and the remainder (9.5%) to miscellaneous causes, of which two may have been suicides. The proportion of suicides among MS deaths was 7.5 times that for the age-matched general population, and the proportion of MS deaths from malignancy was 0.67 times that for the age-matched general population. The proportion of deaths due to malignancy and stroke was the same for the MS patients and the age-matched general population.

Cervical dystonia: Clinical findings and associated movement disorders

Abstract: We studied 300 patients, 61% women, with mean age 49.7 years and mean duration of dystonia 7.8 years, to determine the demographic and clinical characteristics of cervical dystonia (CD) and its relationships to other movement disorders. Torticollis was present in 82%, laterocollis in 42%, retrocollis in 29%, and anterocollis in 25%; however, the majority (66%) had a combination of these abnormal postures. Scoliosis was present in 39%, local pain reported by 68%, and 32% had evidence of secondary cervical radiculopathy. In addition to CD, 16% of patients had oral dystonia, 12% mandibular dystonia, 10% hand/arm dystonia, and 10% had blepharospasm. Tremor was noted in 71% of patients; head-neck tremor was present in 60%, and tremor in other body regions was present in 32%. A family history of a movement disorder was present in 44% of the CD patients. Tardive dystonia was the cause in 6%; 11% had posttraumatic dystonia. Anticholinergic drugs provided moderate improvement in 33% of patients, but local intramuscular botulinum toxin injections relieved CD, local pain, or both in over 90% of all treated patients.

Frontal lobe degeneration: clinical, neuropsychological, and SPECT characteristics.

Abstract: The clinical, neuropsychological, and cerebral blood flow characteristics of eight patients with frontal lobe degeneration (FLD) were studied. Social withdrawal and behavioral disinhibition were the earliest and most common clinical presentations, and psychiatric symptoms typically preceded the onset of dementia by several years. Neuropsychological testing showed selective impairment of frontal and memory tasks with relative sparing of attention, language, and visuospatial skills. Single-photon emission computerized tomography demonstrated frontal and temporal hypoperfusion with relative sparing of parietal and occipital blood flow. Previous studies suggest that the neuropathologic findings in patients with FLD are varied; some demonstrate frontal gliosis, neuronal loss, and Pick bodies while others show only gliosis and neuronal loss.

Essential tremor Clinical correlates in 350 patients

Abstract: To study the demographic and clinical correlates of essential tremor (ET), we analyzed a comprehensive database of 350 patients evaluated at the Movement Disorders Clinic at Baylor College of Medicine from 1982 to 1989. The age at onset of tremor showed bimodal distribution for both male and female patients, with peaks in 2nd and 6th decades. ET appeared most frequently in hands, followed by head, voice, tongue, leg, and trunk. Half of the patients (47%) had associated dystonia including cervical dystonia, writer9s cramp, spasmodic dysphonia, and cranial dystonia, and 20% of the patients had associated parkinsonism. At least one 1st-degree relative of 62.5% of ET patients reported tremor. Alcohol relieved tremor in ± of ET patients. Sixty-eight percent of patients who had adequate follow-up improved with propranolol, and 72% with primidone. There was no significant difference in various clinical variables between the 219 patients with familial ET and 131 with sporadic ET. Patients with early-onset ET were more likely to have hand involvement and associated dystonia than patients with late- onset ET. Dystonia was more frequently associated with mild ET than with severe ET. Patients with low-frequency tremor were older and had more head but less hand involvement than patients with high-frequency tremor. The lack of relevant differences between ET subgroups suggests that, despite variable expression, ET represents a single disease entity.

Interictal spiking during wakefulness and sleep and the localization of foci in temporal lobe epilepsy.

Abstract: We examined variations in interictal spiking during sleep and wakefulness to assess differences in reliability for localizing epileptic foci. Forty patients were studied prospectively. Spikes were assessed for rates, field, and appearance of new foci. Final localization was determined by surgery, electrocorticography, and seizure onset. Comparison of interictal EEG foci with final localization was made. In 39 patients, slow-wave sleep activated spiking compared with wakefulness. Most patients showed maximal spiking in sleep stages 3 or 4. Restriction of field in rapid eye movement (REM) sleep and wakefulness, and extension of field in slow-wave sleep occurred. New foci appeared in non-rapid eye movement sleep in 53% of patients. Similar but not identical spiking rates, foci, and field distributions were seen in wakefulness and REM sleep. All REM foci were unilateral. Our findings suggest that localization of the primary epileptogenic area is more reliable in REM sleep than in wakefulness, and in wakefulness more than in slow-wave sleep.

The clinical features and prognosis of pseudoseizures diagnosed using video‐EEG telemetry

Abstract: A total of 110 patients underwent diagnostic evaluation for attacks of uncertain origin by means of video-EEG telemetry and had a diagnosis of pseudoseizures confirmed. Eighty-six patients (78%) were female, mean age of onset 25 years, and mean duration of attacks was 3 years. Many of the patients had erroneously been thought to be suffering from epilepsy. The attacks could be divided into two broad categories: attacks of collapse (one-third) and attacks with prominent motor activity (two-thirds). In some patients, the attacks were associated with incontinence and injury. The differential diagnosis and clinical features of the attacks are described. Additional psychiatric features were present in 52 (47%) patients. Follow-up (for a median 5 years; range, 1 to 14 years) showed that 40% of these patients stopped having pseudoseizures. This favorable outcome was associated with being female, leading an independent life, a formal psychological approach to therapy and counseling, and the absence of coexisting epilepsy, but not with the duration of pseudoepilepsy, prior episodes of pseudostatus, the coexistence of overt psychiatric disease, or the clinical features of the attacks.

Visuospatial impairment in Parkinson's disease

Abstract: We explored the nature of the visuospatial deficit in Parkinson9s disease (PD) and its progression as a function of disease duration. We compared the performance of 183 patients with idiopathic PD and 90 control subjects matched for age and education on six visuospatial measures. We divided patients into three groups according to the disease duration: early (1 to 4 years), middle (5 to 10 years), and advanced (> 10 years). Performance deteriorated in five of the six visuospatial measures, as a function of disease duration. However, the pattern of visuospatial decline depended on whether dementia was present. The results were not influenced by age or anticholinergic medication. These findings support the presence of visuospatial deficits in PD patients, with a changing pattern of impairment related to dementia and progression of the disease.

Hippocampal degeneration differentiates diffuse Lewy body disease (DLBD) from Alzheimer's disease: Light and electron microscopic immunocytochemistry of CA2–3 neurites specific to DLBD

Abstract: Immunocytochemistry with antibodies to ubiquitin is currently the most sensitive method for detecting cortical Lewy bodies, which are a sine qua non for the diagnosis of diffuse Lewy body disease (DLBD), an increasingly recognized form of primary degenerative dementia. In the systematic application of ubiquitin immunocytochemistry to sections of hippocampus from control subjects and patients with a wide spectrum of neurodegenerative diseases, we noted the frequent occurrence of ubiquitin-immunoreactive neurites in the CA2-3 region in DLBD. The nature of these neurites was investigated with immunocytochemistry in DLBD, Alzheimer's disease (AD), normal elderly subjects, and Parkinson's disease (PD). Although the number of neurites varied from case to case, they were virtually always detected in DLBD but not in normal, AD, or PD brains. Double immunolabeling studies with anti-ubiquitin demonstrated a small fraction of double-stained neurites with antibodies to neurofilament or Alz-50, but no double staining with an antibody to Alzheimer neurofibrillary tangles. These results are different from those for neurites in AD, which are rarely seen in CA2-3 and which are immunoreactive with all these antibodies. Neuritic degeneration in the CA2-3 region of the hippocampus appears to be a specific histopathologic feature of DLBD.

The Rochester Diabetic Neuropathy Study Design, criteria for types of neuropathy, selection bias, and reproducibility of neuropathic tests

Abstract: A cross-sectional survey and subsequent longitudinal study among diabetic residents of Rochester, MN- The Rochester Diabetic Neuropathy Study (RDNS)-is population-based and uses quantitative, validated, and unique end points to detect, classify, and stage neuropathy. Nondiabetic persons, drawn from the same population, serve as controls. For patients 10 to 70 years old, the RDNS cohort is representative of diabetics living in Rochester, MN. We assessed reproducibility of tests used to characterize and quantitate severity of neuropathy in 20 diabetic subjects without neuropathy and with varying severities of neuropathy. Using intraclass correlation coefficient (r 1 ) as a measure of test reproducibility, we found high r 1 (usually 0.9 or better) with small confidence intervals for the Neurologic Disability Score (NDS); weakness subset of NDS (W-NDS); vibratory and cooling detection thresholds (using computer-assisted sensory examination [CASE] IV); compound muscle action potentials; sensory nerve action potentials; and motor nerve conduction velocities. There was good agreement among three trained observors for NDS and the W-NDS.

Early development of levodopa-induced dyskinesias and response fluctuations in young-onset Parkinson's disease.

Abstract: We evaluated whether patients with young-onset Parkinson9s disease (PD) (onset between 21 and 40 years) develop levodopa-induced dyskinesias and motor response fluctuations more frequently and earlier than patients with older- onset PD (onset after 40 years) by determining the period from levodopa introduction to development of dyskinesias or fluctuations in 25 young-onset (mean age at onset, 33.54 years) and in 25 matched older-onset PD patients (mean age at onset, 55.76 years). Young-onset PD patients had significantly higher frequency for both dyskinesias and fluctuations after both 3 and 5 years of levodopa. Young-onset PD patients also developed both levodopa-induced dyskinesias and fluctuations earlier than older-onset PD patients. We suggest that the introduction of levodopa therapy in patients with young-onset PD should be postponed as long as possible.

Hashimoto's encephalopathy: a steroid-responsive disorder associated with high anti-thyroid antibody titers--report of 5 cases.

Abstract: We describe 5 patients with a relapsing encephalopathy in association with Hashimoto's disease and high titers of anti-thyroid antibodies. The presentation is usually with a subacute onset of confusion, alteration in conscious level, and focal or generalized seizures. The relapsing course, association with myoclonus or tremulousness, and episodes of stroke-like deterioration are characteristic features. The long-term prognosis is favorable with steroid therapy, though additional immunosuppressive therapy may be required. Neurologic investigation typically shows a diffusely abnormal EEG, high CSF protein level without pleocytosis, and normal brain CT and cerebral angiogram. Isotope brain scan may show patchy abnormal uptake. Hashimoto's encephalopathy should be recognized as a definite neurologic entity and added to the list of CNS complications of thyroid disease.

Effects of transcranial magnetic stimulation on ipsilateral muscles

Abstract: We studied the effects of transcranial magnetic stimulation of the motor cortex on ipsilateral upper extremity muscles in six normal men. Stimulation had inhibitory and excitatory effects on the muscles during voluntary activation. Transient inhibition, an ipsilateral silent period (ISP), occurred in all muscles tested, often without any preceding excitatory response. Motor evoked potentials (MEPs) occurred ipsilaterally in the proximal muscles of some subjects. Ipsilateral MEPs and ISPs were delayed relative to the MEPs evoked by the same stimulus in the corresponding contralateral muscles. The excitability of the alpha motoneuron pool, assessed during the period of the ISP by eliciting H-reflexes, showed no change, suggesting that ipsilateral inhibition acts at a level above the alpha motoneuron. Connections from motor cortex to ipsilateral muscles could be via the corpus callosum and contralateral hemisphere or via purely ipsilateral pathways.

Parkinson's disease rigidity: Magnetic motor evoked potentials in a small hand muscle

Abstract: We studied the EMG potentials evoked in the bilateral first dorsal interosseus muscle by electromagnetic stimulation of the corticomotoneuronal descending system in 10 Parkinson's disease patients and in 10 age- and sex-matched normal controls. We selected patients who did not have tremor but had predominant rigidity with asymmetric body involvement. On the rigid side of the PD patients, the threshold to cortical stimulation was lower than on the contralateral side or than normal values. On average, patients had normal central conduction times, but their motor evoked potentials (MEPs) on the rigid side were larger than those of controls when the cortical stimulus was at rest or during slight tonic contraction of the target muscle. In the latter condition, a silent period shorter than that of controls followed MEPs, whereas the peripheral silent period following ulnar nerve stimulation at the wrist was prolonged. Alpha motor neuron excitability, tested by the F-wave method, was enhanced on the rigid side at rest. In rigidity, spinal motor nuclei may be more responsive than normal to descending inputs from motor cortex, or the entire corticomotoneuron system may prove hyperexcitable under given conditions.

Reorganization of corticospinal pathways following spinal cord injury.

Abstract: To assess changes in the relationship between cortical motor representation areas and their target muscles following spinal cord lesions, we studied motor evoked potentials (MEPs) to transcranial magnetic stimulation in six patients with complete spinal cord injuries at low thoracic levels and eight healthy subjects. Magnetic stimulation at rest activated a larger fraction of the motoneuron pool and evoked MEPs with shorter latencies from a larger number of scalp positions in muscles immediately rostral to the level of a spinal cord injury than in corresponding muscles in controls. The MEPs associated with maximal voluntary activation were not significantly different in the two groups. These results suggest enhanced excitability of motor pathways targeting muscles rostral to the level of a spinal transection, reflecting reorganization of motor pathways either within cortical motor representation areas or at the level of the spinal cord. The data do not allow the determination of the contribution of spinal or cortical mechanisms. However, they support the notion of a limited flexible relationship between primary motor cortex and its target muscles following alterations of normal input-output patterns.

Long-term benefit from prednisone therapy in Duchenne muscular dystrophy

Abstract: Two successive, 6-month, randomized, double-blind, controlled trials of prednisone showed that 0.75 mg/kg/d was the optimal dose to improve strength in boys with Duchenne muscular dystrophy (DMD). We attempted to maintain 93 boys on that dose for an additional 2 years. During the 3 years of observation, the decline in average muscle strength scores of all boys taking prednisone was 0.072 units/yr, as compared with an expected decline of 0.341 units/yr from natural history controls. The occurrence of side effects in some boys prevented maintenance of the full dose, which may have lessened the response. At the time of last visit, dosages ranged from 0.15 mg/kg to 0.75 mg/kg. In addition to maintaining their strength, several of the boys actually improved their performance in lifting kilogram weights and in some timed function tests. Treatment of DMD with prednisone significantly slows the progression of weakness and loss of function for at least 3 years.

Expression of heat shock proteins in Alzheimer's disease

Abstract: In an investigation of heat shock proteins (HSPs) in the brains of Alzheimer9s disease (AD) patients and cognitively intact control subjects, we found that 2 HSPs, termed “HSP72” and “GRP78,” underwent major changes in expression in AD. HSP72, which was present at very low levels in control brains, increased dramatically in AD patients, and was localized exclusively in neuritic plaques and neurofibrillary tangles. We hypothesize that HSP72 is induced as an early response to the formation of abnormal proteins, perhaps targeting them for proteolysis. In contrast, GRP78 increased in AD only in neurons that remained cytologically normal, especially in the CA3 subfield of the hippocampus and the deep layers of the entorhinal cortex. The increased expression of GRP78 within successfully surviving neurons suggests that this protein may protect such cells from AD-specific damage.