Wasted leg syndrome: An atypical slowly-progressive form of lower motor neuron disease.

We describe four male patients with wasted-leg syndrome, with predominant asymmetric thigh atrophy and weakness that stabilized after a period of slow progression (follow-up 7-18 years). Two patients had an Indian ethnic background and two were Portuguese, without known Indian ancestry. Other mimicking disorders were excluded, but one Indian patient was later diagnosed with CADASIL. Electromyography (EMG) revealed severe chronic neurogenic changes in proximal leg muscles, and mild changes in distal leg muscles, but EMG of the upper limbs was normal. Upper motor neuron signs were absent clinically and on transcranial magnetic stimulation. This seems to represent a variant of the common wasted-leg syndrome presentation.

Muscular cramp: causes and management.

Muscular cramp is a common symptom in healthy people, especially among the elderly and in young people after vigorous or peak exercise. It is prominent in a number of benign neurological syndromes. It is a particular feature of chronic neurogenic disorders, especially amyotrophic lateral sclerosis. A literature review was undertaken to understand the diverse clinical associations of cramp and its neurophysiological basis, taking into account recent developments in membrane physiology and modulation of motor neuronal excitability. Many aspects of cramping remain incompletely understood and require further study. Current treatment options are correspondingly limited.

Plasma level of club-cell (CC-16) predicts outcome in amyotrophic lateral sclerosis.

OBJECTIVES: The club cell protein (CC-16) is a biomarker associated with respiratory distress and pulmonary inflammation. We evaluated CC-16 as a candidate biomarker for respiratory failure in amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: We studied 81 ALS patients and 30 matched controls. We used an ALS-related measure of functional capacity, and tested forced vital capacity (FVC) and the amplitude of the diaphragmatic response by phrenic nerve stimulation (PhrenAmpl). Plasma CC-16 levels were measured in venous blood. Kaplan-Meier survival curves were plotted to evaluate risk to non-invasive ventilation and death in patients with abnormal CC-16 levels. RESULTS: CC-16 levels were significantly raised in ALS patients (10.56 ng/mL ± 6.84 vs 8.34 ng/mL ± 3.10, P = .02), and in 17% of them, CC-16 level was above the upper cutoff value (mean + 2.5SD). CC-16 levels did not correlate with age, onset region, disease duration, functional status, FVC, and PhrenAmpl. In patients with increased CC-16 level, the risk of non-invasive was greater in the following 6 months (P = .01) and tended to have higher mortality in the following 30 months (P = .07). CONCLUSIONS: We propose that increased CC-16 levels is a marker of lung inflammatory response that associated with ventilatory insufficiency are related to impending respiratory failure, not fully predicted by conventional respiratory tests. The latter are limited by the moment of testing.

Defecation 2: Internal anorectal resistance is a critical factor in defecatory disorders.

BACKGROUND: The aim of this study was to test our hypothesis that the reason why imaging is of little assistance in diagnosing "constipation" causes may be related to the high sensitivity of internal anorectal flow resistance in defecation to small changes in geometry. We applied a mathematical model to describe the effects on flow mechanics of observed changes in the shape of the rectum and anus during defecation. METHODS: Three groups of patients were studied with video proctograms. Group 1 comprised 4 patients with normal defecation studied with video proctography or magnetic resonance imaging (MRI). Group 2 comprised 8 patients with fecal incontinence, studied by video X-ray electromyography. Group 3 comprised 8 patients with constipation evaluated by video MRI. RESULTS: Three muscle vectors open the anorectal angle prior to defecation, causing the anorectal luminal diameter to increase to approximately twice its resting size. These vectors are forwards (anterior wall), backwards and downwards (posterior wall). Resistance to passage of a fecal bolus through the anorectum is determined by viscous friction against the anorectal wall and by the energy required to deform the bolus as it flows. The observed changes in anorectal geometry serve to reduce both the viscous friction in the anus and the deformation of the bolus, which reduces the force required to facilitate its passage through the anus. For example, if the effective diameter of the anus is doubled during defecation, the frictional resistance is reduced by a factor of 8. CONCLUSIONS: The sensitivity of flow resistance to geometry explains why MRI or computed tomography (CT) scans taken during defecation are not often helpful in diagnosing causation. Small changes in geometry can have a disproportionate affect on flow resistance. Combining accurate directional measurements during dynamic MRI or CT scans taken during defecation with observations of bolus deformation, and if possible, simultaneous anorectal manometry, may provide clinically helpful insights on patients with anorectal evacuation disorders.

Defecation 1: Testing a hypothesis for pelvic striated muscle action to open the anorectum.

BACKGROUND: We conducted an observational study to assess the hypothesis that the pelvic muscles actively open the anorectal lumen during defecation. METHODS: Three groups of female patients were evaluated with video imaging studies of defecation using a grid or bony reference points. Eight patients with idiopathic fecal incontinence had video myogram defecography; eight with obstructive defecation had magnetic resonance imaging (MRI) defecating proctograms; and four normal patients had video X-ray or MRI defecating proctogram studies. RESULTS: In all three groups, the anorectum was stretched bidirectionally by three directional muscle force vectors acting on the walls of the rectum, effectively doubling the diameter of the rectum during defecation. The anterior rectal wall was pulled forwards, and the posterior wall backwards and downwards opening the anorectal angle, associated with angulation of the anterior tip of the levator plate (LP). These observations are consistent with a staged relaxation of some parts of the pelvic floor during defecation, and contraction of others. First, the puborectalis muscle relaxes. Puborectalis muscle relaxation frees the posterior rectal wall so that it can be stretched and opened by contraction of the LP and conjoint longitudinal muscle of the anus. Second, contraction of the pubococcygeus muscle pulls forward the anterior rectal wall, further increasing the diameter of the rectum. Third, when the bolus has entered the rectum, the external anal sphincter relaxes, and the rectum contracts to expel the fecal bolus. CONCLUSIONS: Our results are consistent with the hypothesis that pelvic striated muscle actively opens the rectal lumen, thereby reducing internal anorectal resistance to expulsion of feces. Controlled studies of electromyographic activity would be useful to further test this hypothesis.

Regional changes of ciliary neurotrophic factor and nerve growth factor levels in post mortem spinal cord and cerebral cortex from patients with motor disease.

Ciliary neurotrophic factor (CNTF) rescues motor neurons in animal models of injury and neurodegeneration, and disruption of the mouse CNTF gene results in motor neuron degeneration in mature adults. Glial cells increase nerve growth factor (NGF) expression in neuropathological conditions, and the sensory system can be affected in the amyotrophic lateral sclerosis (ALS) type of motor neuronic disease. We therefore studied CNTF and NGF levels in post mortem spinal cord and cerebral cortex from patients with ALS and matched controls. We report a marked decrease of CNTF in the ventral horn of spinal cord in ALS, with no change in cerebral motor cortex. In contrast, NGF levels were decreased in ALS cerebral motor cortex, where the corticospinal tract originates, but increased in the lateral column of spinal cord, which includes the region of corticospinal tract degeneration in ALS. Both CNTF and NGF levels were decreased in ALS dorsal spinal cord.

Diagnostic criteria for amyotrophic lateral sclerosis: A multicentre study of inter-rater variation and sensitivity.

OBJECTIVE: This study assesses inter-rater agreement and sensitivity of diagnostic criteria for amyotrophic lateral sclerosis (ALS). METHODS: Clinical and electrophysiological data of 399 patients with suspected ALS were collected by eleven experienced physicians from ten different countries. Eight physicians classified patients independently and blinded according to the revised El Escorial Criteria (rEEC) and to the Awaji Criteria (AC). Inter-rater agreement was assessed by Kappa coefficients, sensitivity by majority diagnosis on 350 patients with follow-up data. RESULTS: Inter-rater agreement was generally low both for rEEC and AC. Agreement was best on the categories "Not-ALS", "Definite", and "Probable", and poorest for "Possible" and "Probable Laboratory-supported". Sensitivity was equal for rEEC (64%) and AC (63%), probably due to downgrading of "Probable Laboratory-supported" patients by AC. However, AC was significantly more effective in classifying patients as "ALS" versus "Not-ALS" (p < 0.0001). CONCLUSIONS: Inter-rater variation is high both for rEEC and for AC probably due to a high complexity of the rEEC inherent in the AC. The gain of AC on diagnostic sensitivity is reduced by the omission of the "Probable Laboratory-supported" category. SIGNIFICANCE: The results highlight a need for initiatives to develop simpler and more reproducible diagnostic criteria for ALS in clinical practice and research.

Exertional myocardial ischemia in diabetes: a quantitative analysis of anginal perceptual threshold and the influence of autonomic function.

Patients with diabetes are prone to silent myocardial infarction and silent exertional ischemia. Although the mechanism is not clear, it may reflect a specific impairment of the sensory innervation of the heart. To test this hypothesis, anginal perceptual threshold was measured in 32 diabetic patients and 36 nondiabetic control patients, all of whom had typical exertional angina. Anginal perceptual threshold was defined as the time from onset of 0.1 mV ST depression to the onset of chest pain during treadmill stress electrocardiography. Although ST depression occurred earlier in the diabetic than in the nondiabetic group (111 +/- 82 versus 216 +/- 162 s, p less than 0.005), the anginal perceptual threshold in the diabetic group was delayed by a mean of 86 s (149 +/- 76 versus 63 +/- 59 s, p less than 0.001), with 95% confidence intervals of 53 to 119 s. Autonomic function tests were abnormal in the diabetic group, and in both groups regression analyses (using a third order polynomial) showed marked prolongations of anginal perceptual threshold as the heart rate responses to the Valsalva maneuver decreased to below the normal range (r = 0.5, p less than 0.001). There was a similar though less pronounced relation between anginal perceptual threshold and the heart rate responses to deep breathing (r = 0.3, p less than 0.02). These data suggest that prolongation of the anginal perceptual threshold may be caused by autonomic neuropathy involving the sensory innervation of the heart. To test sensory function, median nerve conduction studies were performed in 19 patients (10 diabetic and 9 nondiabetic).(ABSTRACT TRUNCATED AT 250 WORDS)

Recognition memory in Alzheimer's disease.

Recognition memory for several types of stimulus material was examined in patients clinically diagnosed as having early Alzheimer's disease and in normal elderly controls. Although performance deficits were demonstrated for verbal and abstract stimuli (geometric shapes and histology slides), memory for faces was relatively intact in the patient group. Patients made more false positive responses than controls, but this could not be accounted for by a general disinhibition of responding. It is suggested that a contextual processing deficit may explain the pattern of false positive responding and this is discussed in relation to previous findings of drug studies in Alzheimer's disease.

Parity as a factor in incontinence in multiple sclerosis.

Twelve consecutively selected patients with multiple sclerosis and incontinence had electrophysiologic studies performed of the pudendal and perineal innervations of the anal and urinary sphincter. Single-fiber electromyogram density measurements were obtained in the external anal sphincter. Fecal incontinence was found to be unexpectedly frequent. The results suggest that incontinence in patients with multiple sclerosis is often due to the interaction of several factors, including central lesions, lesions of the conus medullaris and, also, coincidental pelvic nerve lesions associated with childbirth. Thus, incontinence is especially a problem in women with this disease.

Carcinoid myopathy. Serotonin-induced muscle weakness in man?

A myopathy, which improved with cyproheptadine hydrochloride therapy, developed in a patient with carcinoid syndrome of ten years' duration. Biopsy examination revealed advanced atrophy of type II muscle fibers, with type I fiber preponderance. Many of the small fibers had degenerated. Carcinoid myopathy may be due to excess circulating serotonin.

Neurologic cause of idiopathic incontinence.

The relationship between the pudendal and perineal nerve terminal motor latencies and descent (weakness) of the perineum on straining was investigated in 31 patients with idiopathic fecal incontinence, and in 30 patients with double incontinence. Pelvic floor descent was correlated with increased pudendal nerve terminal motor latency in both groups of patients. In the patients with double incontinence, there was a less significant correlation between perineal descent and increased perineal nerve terminal motor latency. In the patients with fecal incontinence, but without urinary incontinence, there was no correlation between perineal descent and perineal nerve terminal motor latency. These data support the concept that pelvic floor weakness can result in damage to the pudendal and perineal nerves, leading to fecal and urinary incontinence. In patients with isolated fecal incontinence the perineal nerves are relatively spared. Thus these common types of incontinence probably have a neurologic cause, and neurophysiologic methods can be used in their assessment.

Small deep cerebral infarcts associated with occlusive internal carotid artery disease. A hemodynamic phenomenon?

Small deep cerebral infarcts, often referred to as lacunes, have been traditionally associated with small-vessel disease affecting the deep penetrating arterial system. We describe 10 cases where these infarcts were associated with severe, ipsilateral internal carotid artery occlusive disease. Seven of these patients also had severe occlusive disease of the contralateral internal carotid artery. The clinical and radiologic features, in combination with studies of cerebral blood flow, were consistent with hemodynamically mediated cerebral ischemia. Occlusive internal carotid artery disease may be more commonly associated with hemodynamic cerebral ischemia than previously believed, and small cerebral infarcts in the deep arterial border zone areas are likely to be an important manifestation of this process.

Anal sphincter dysfunction in Parkinson's disease.

Striated anal sphincter function was studied electrophysiologically and radiologically in six patients with Parkinson's disease and chronic constipation. In five cases, there was paradoxic anal sphincter muscle contraction during simulated defecation straining resembling anismus-type pelvic outlet obstruction. Radiologic studies showed functional improvement of the defecatory mechanism following the administration of the dopamine receptor agonist apomorphine in four patients. Dysfunction of the striated anal sphincter musculature may be a significant cause of constipation in some parkinsonian patients, occurring as part of the generalized extrapyramidal motor disorder.

An algorithm for ALS diagnosis and management.

The diagnosis of ALS is often delayed, probably largely because the disease is relatively uncommon. A practical approach to diagnosis, with a simple algorithm for investigation, might improve diagnostic sensitivity in the early stages of the disease. It is clear that the first step in the diagnostic algorithm must be referral to a neurologist, which implies recognition by the primary care physician that the illness is neurologic in origin. It is the role of the neurologist to make the diagnosis, to confirm it beyond all reasonable doubt, to exclude other treatable conditions, and to inform the patient and the family of the diagnosis in a timely, honest, and compassionate way. Definition of different disease stages allows a model of the process of care to be formulated and indicates the time points at which intervention may be possible. There are two pathways to diagnosis of ALS, which overlap to a considerable extent. Diagnosis by positive criteria is limited by the absence of a specific diagnostic test, whereas diagnosis by exclusion of other disorders may introduce delay that can be tempered only by efficiency in the investigative pathway. The imperative necessity for diagnostic review is perhaps the most important aspect of the diagnosis of ALS, in view of the increasing recognition of the need for early diagnosis, and when an effective therapy becomes available, this process of review will become more important, albeit more difficult.