EFNS guidelines on the use of neuroimaging in the management of motor neuron diseases.

BACKGROUND AND PURPOSE: These European Federation of Neurological Societies guidelines on neuroimaging of motor neuron diseases (MNDs) are designed to provide practical help for the neurologists to make appropriate use of neuroimaging techniques in patients with MNDs, which ranges from diagnostic and monitoring aspects to the in vivo study of the pathobiology of such conditions. METHODS: Literature searches were performed before expert members of the Task Force wrote proposal. Then, consensus was reached by circulating drafts of the manuscript to the Task Force members and by discussion of the classification of evidence and recommendations. RESULTS AND CONCLUSIONS: The use of conventional MRI in patients suspected of having a MND is yet restricted to exclude other causes of signs and symptoms of MN pathology [class IV, level good clinical practice point (GCPP)]. Although the detection of corticospinal tract hyperintensities on conventional MRI and a T2-hypointense rim in the pre-central gyrus can support a pre-existing suspicion of MND, the specific search of these abnormalities for the purpose of making a firm diagnosis of MND is not recommended (class IV, level GCPP). At present, advanced neuroimaging techniques, including diffusion tensor imaging and proton magnetic resonance spectroscopic imaging, do not have a role in the diagnosis or routine monitoring of MNDs yet (class IV, level GCPP). However, it is strongly advisable to incorporate measures derived from these techniques into new clinical trials as exploratory outcomes to gain additional insights into disease pathophysiology and into the value of these techniques in the (longitudinal) assessment of MNDs (class IV, level GCPP).

"Ears of the Lynx" MRI Sign Is Associated with SPG11 and SPG15 Hereditary Spastic Paraplegia.

BACKGROUND AND PURPOSE: The "ears of the lynx" MR imaging sign has been described in case reports of hereditary spastic paraplegia with a thin corpus callosum, mostly associated with mutations in the spatacsin vesicle trafficking associated gene, causing Spastic Paraplegia type 11 (SPG11). This sign corresponds to long T1 and T2 values in the forceps minor of the corpus callosum, which appears hyperintense on FLAIR and hypointense on T1-weighted images. Our purpose was to determine the sensitivity and specificity of the ears of the lynx MR imaging sign for genetic cases compared with common potential mimics. MATERIALS AND METHODS: Four independent raters, blinded to the diagnosis, determined whether the ears of the lynx sign was present in each of a set of 204 single anonymized FLAIR and T1-weighted MR images from 34 patients with causal mutations associated with SPG11 or Spastic Paraplegia type 15 (SPG15). 34 healthy controls, and 34 patients with multiple sclerosis. RESULTS: The interrater reliability for FLAIR images was substantial (Cohen κ, 0.66-0.77). For these images, the sensitivity of the ears of the lynx sign across raters ranged from 78.8 to 97.0 and the specificity ranged from 90.9 to 100. The accuracy of the sign, measured by area under the receiver operating characteristic curve, ranged from very good (87.1) to excellent (93.9). CONCLUSIONS: The ears of the lynx sign on FLAIR MR imaging is highly specific for the most common genetic subtypes of hereditary spastic paraplegia with a thin corpus callosum. When this sign is present, there is a high likelihood of a genetic mutation, particularly associated with SPG11 or SPG15, even in the absence of a family history.

A patient with MV2 subtype of sporadic Creutzfeldt-Jakob disease and atypical clinical presentation.

We report the case of a 71-year-old woman with progressive dementia over the course of 4 years, characterized by prominent pyramidal signs and by the lack of ataxia and other cerebellar signs. Creutzfeldt-Jakob disease (CJD) was not suspected during the patient's life. Autopsy brain tissue showed severe spongiform encephalopathy with kuru-like, but not florid, plaques in neocortex and cerebellum. Massive synaptic diffuse and plaque-like PrP(Sc) deposition was found in the cerebral cortex, striatum, cerebellum and brainstem. Genetic analysis revealed no PRNP gene mutations and methionine/valine heterozygosity (MV) at codon 129. The pathogenic scrapie prion protein (PrP(Sc)) pattern detected by Western blot was Type 2. However, this pattern showed a single unglycosylated band in contrast to the doublet described for MV2 subtype of sCJD with kuru plaques. In summary, this is an autopsy case report of a particular presentation of MV2 subtype of sCJD.

EFNS guideline on neuroimaging in acute stroke. Report of an EFNS task force.

Neuroimaging techniques are necessary for the evaluation of stroke, one of the leading causes of death and neurological impairment in developed countries. The multiplicity of techniques available has increased the complexity of decision making for physicians. We performed a comprehensive review of the literature in English for the period 1965-2005 and critically assessed the relevant publications. The members of the panel reviewed and corrected an initial draft, until a consensus was reached on recommendations stratified according to the European Federation of Neurological Societies (EFNS) criteria. Non-contrast computed tomography (CT) scan is the established imaging procedure for the initial evaluation of stroke patients. However, magnetic resonance imaging (MRI) has a higher sensitivity than CT for the demonstration of infarcted or ischemic areas and depicts well acute and chronic intracerebral hemorrhage. Perfusion and diffusion MRI together with MR angiography (MRA) are very helpful for the acute evaluation of patients with ischemic stroke. MRI and MRA are the recommended techniques for screening cerebral aneurysms and for the diagnosis of cerebral venous thrombosis and arterial dissection. For the non-invasive study of extracranial vessels, MRA is less portable and more expensive than ultrasonography but it has higher sensitivity and specificity for carotid stenosis. Transcranial Doppler is very useful for monitoring arterial reperfusion after thrombolysis, for the diagnosis of intracranial stenosis and of right-to-left shunts, and for monitoring vasospasm after subarachnoid hemorrhage. Currently, single photon emission computed tomography and positron emission tomography have a more limited role in the evaluation of the acute stroke patient.

The role of single photon emission computed tomography brain imaging with 99mTc-bicisate in the localization and definition of mechanism of ischemic stroke.

99mTc-bicisate (99mTc-ECD) is a new brain perfusion imaging agent formulated from a radiochemically stable kit (Neurolite). A multicenter trial was conducted to determine the sensitivity and specificity of single photon emission computed tomography (SPECT) imaging with 99mTc-bicisate in the localization of ischemic stroke; 170 subjects were enrolled, 128 patients with stroke and 42 controls. Imaging results from 148 subjects (107 stroke patients and 41 controls) were considered evaluable. In the evaluable subjects, SPECT brain imaging with 99mTc-bicisate (21.0 +/- 2.5 mCi) was interpreted without clinical information and was compared with a final assessment using all clinical, diagnostic, and laboratory procedures except the 99mTc-bicisate SPECT results. 99mTc-bicisate was safe and well-tolerated. SPECT imaging with 99mTc-bicisate demonstrated a specificity of 98% and a sensitivity of 86% for localization of strokes (kappa, 0.75; 95% confidence interval, 0.64-0.86). Results were unchanged over time and were similar for all stroke mechanisms except for lacunar disease (sensitivity, 58%). In a secondary analysis, a normal image or small, deep (e.g., subcortical) perfusion defect was highly predictive of a lacunar mechanism. Defects involving the cortical surface were strongly associated with nonlacunar mechanisms. SPECT imaging with 99mTc-bicisate is a sensitive marker in the localization of perfusion defects associated with ischemic stroke and may assist in the determination of the underlying mechanism of a stroke.

Extrapyramidal symptoms due to dopamine-blocking agents in patients with AIDS encephalopathy.

OBJECTIVE: The authors attempted to determine whether patients with AIDS are more susceptible to neuroleptic side effects than other patients. METHOD: Retrospective chart review was used to assess the frequency and severity of extrapyramidal symptoms in patients with AIDS and psychotic patients without AIDS who had taken dopamine-blocking agents. The charts of 804 men younger than 50 years were reviewed, and patients were excluded if they had not taken dopamine blockers, had taken them for more than 1 month, had received concomitant antiparkinsonian agents, had focal brain lesions or histories of Parkinson's disease or meningitis, had used cocaine, amphetamines, or opiates within 1 month of admission, or, among the comparison group, had HIV risk factors. For the remaining 31 AIDS and 32 comparison patients, age, duration of dopamine blocker treatment, dose in chlorpromazine equivalents, and nature and severity of parkinsonian complications were recorded. RESULTS: The mean drug dose and body weight were significantly lower in the AIDS group. The likelihood of developing extrapyramidal symptoms was 2.4 times as high among the AIDS patients as among the comparison group. Such symptoms were developed by 50% of the AIDS patients who received less than 4 mg/kg of chlorpromazine equivalents per day and 78% of those who received more than 4 mg/kg per day. CONCLUSIONS: These preliminary results suggest that AIDS patients are more susceptible to extrapyramidal symptoms than psychotic patients without AIDS and that neuroleptics should be used cautiously and in lower doses for patients with AIDS.

Autonomic dysfunction and sleep apnea in olivopontocerebellar degeneration.

We studied ten men with olivopontocerebellar degeneration. Our findings of the autonomic deficits as manifested by orthostatic hypotension, impaired Valsalva's response, abnormal findings on cold pressor and mental arithmetic tests, and plasma renin and norepinephrine abnormalities in some patients with olivopontocerebellar degeneration suggested a defective central control of the sympathetic nervous system. Five patients had sleep apnea. Autonomic dysfunction and sleep apnea in olivopontocerebellar degeneration may result from degenerative lesions in the cerebellum and the brain stem.

Delayed radiation necrosis of the brain contralateral to original tumor.

In a 23-year-old man, radiation necrosis developed in the left hemisphere after radiation of a right-sided intracranial tumor. Since normal tissue had to be resected around the tumor, the contralateral temporal lobe received the highest cumulative radiation dose for brain tissue. This report underscores the need for careful reconstruction of the radiation isodose distribution when considering the differential diagnosis of postradiation brain lesions.

Evaluation of recent cerebral infarction by computerized tomography.

Twenty patients with cerebral infarction were observed with serial computerized tomographic (CT) scans. Seventy percent of those infarctions showed a mass effect that had disappeared in all patients by the eighth week after the ictus. In 63%, there was enhancement after contrast infusion, with a definite temporal relationship to the day of onset of the neurological deficit. Twenty percent of the patients initially had normal CT scans that became abnormal weeks after the stroke. Radionuclide scans were positive in the patients who showed contrast enhancement, and the area of abnormal uptake correlated well with the area of enhancement. The timing of the performance of the CT scan in relation to the onset of neurological deficit is an important factor to consider when evaluating the stroke syndrome with CT.

Brain white-matter changes in the elderly prone to falling.

Falls and impaired gait are a major source of morbidity in the elderly. Why some elderly become prone to falling is often unclear. We analyzed the gait, equilibrium, and brain computed tomography results of 40 elderly subjects without evidence of neurologic disease known to be associated with falls. Twenty of these subjects were prone to falling and the remaining 20 were nonfalling controls. These two groups were comparable in terms of age and sex (mean age, 83.3 years [SE, 1.7 years]). The group of fallers had significantly worse gait and equilibrium scores and a greater degree of white-matter hypodensity on computed tomography. White-matter hypodensity correlated with impaired gait and equilibrium scores but not with impaired performance on cognitive testing. This study reveals the association of white-matter disease with gait and balance impairment leading to falls in the elderly.

Inclusion body myositis. A corticosteroid-resistant idiopathic inflammatory myopathy.

In seven patients with slowly progressive muscle weakness, inclusion body myositis (IBM) was diagnosed on biopsy. None had stigmata of collagen-vascular disease or malignancy. Serum creatine kinase levels were mildly or moderately increased. The six patients treated with prednisone did not improve. Needle electromyography showed a "myopathic" pattern in all patients, but four also had diffuse neurogenic changes with normal nerve conductions. Histologic study of muscle showed a mixture of small rounded fibers varying in size, atrophic angulated fibers forming small groups, and hypertrophic fibers. Variable amounts of inflammation, necrosis, and regeneration were seen in all specimens. All showed numerous intracytoplasmic vacuoles lined with purple-blue granules. Electron microscopy showed membranous whorls and masses of abnormal filaments measuring 14 to 18 nm in diameter. Although IBM seems to be a distinct type of inflammatory myopathy, its etiology and pathogenesis are not clear.

Enhancing mass on CT: neoplasm or recent infarction?

On CT, mass effect and contrast enhancement have limited value in separating brain neoplasm from infarct, because both findings are frequent with recent infarction. Review of CT in 100 patients with histologically proven supratentorial lesions (35 infarcts and 65 tumors) indicated the specificity of three helpful signs: (1) White matter edema outlined the uninvolved cortex in 73% of metastases and in 74% of gliomas but only in 14% of infarcts. (2) The cortical ribbon was enhanced in 43% of infarcts, in 7% of gliomas, and in 4% of metastases. (3) Selective sparing of the thalamus occurred in 31% of infarcts but only in 7% of tumors.

Management of lobar intracerebral hemorrhage: medical or surgical.

Two case histories of left parietal hemorrhage, with CTs, were evaluated by 88 board-certified neurologists and 114 board-certified neurosurgeons. Among the neurologists, 24% would have referred both patients for removal of the hemorrhage, 24% would have referred one of them, and 52% would have referred neither. Among the neurosurgeons, 47% would have operated on both patients, 25% on one of them, and 28% on neither. The lack of consensus probably results from an imperfect understanding of the natural history of these lesions. Controlled studies, or at least large retrospective studies, are needed to clarify this important therapeutic issue.

Incidence of seizures with phenytoin toxicity.

Among 50 patients with phenytoin intoxication, 14 had seizures during the episode. Seizures in 9 of these 14 patients probably resulted from poor seizure control despite high phenytoin levels, but in 5 cases, attacks were attributed to phenytoin toxicity. The only factor that seemed to correlate with seizures was a serum phenytoin level over 30 micrograms/ml. No demographic, metabolic, neuropsychiatric, or therapeutic variables were predictive; nor were any other symptoms of toxicity particularly likely to be found in association with seizures. Seizures are an occasional manifestation of phenytoin toxicity, particularly when levels are high.

Medullary satiety.

A 62-year-old man with a tegmental medullary glioma lost 30 pounds of weight in several months because of lack of appetite and early satiety. The medullary tegmentum may play an important role in regulating feeding behavior in humans.

Posttraumatic delayed sleep phase syndrome.

Circadian rhythm sleep disorders may occur after traumatic brain injury. We describe a 48-year-old man who presented with sleep onset insomnia and cognitive dysfunction after a car accident. A diagnosis of delayed sleep phase syndrome (DSPS) was confirmed by sleep logs and actigraphy, which revealed sleep onset in the early morning hours and awakening around noon.

Motor aphasia unaccompanied by faciobrachial weakness.

Most patients with motor aphasia resulting from lesions of the left frontal opercular region have weakness of the right face and arm. We report a 43-year-old man who suffered mutism and agraphia unaccompanied by right-sided weakness after embolic infarction of Broca's area.

Thalamic neuroaxonal dystrophy and dementia in Hodgkin's disease.

The brain of a patient with Hodgkin's disease and dementia showed numerous dystrophic axons in the thalamus. In absence of lymphomatous cellular infiltration, necrosis, hemorrhage, demyelination, neuronal loss, or infection by opportunistic organisms, the axonal dystrophy in this patient appeared to be directly related to the Hodgkin's disease itself. Moreover, dementia as a nonmetastatic complication of Hodgkin's disease may have been the result of the thalamic axonal dystrophy.

Aphasia following infarction of the left supplementary motor area: a clinicopathologic study.

The speech disturbance of a patient with a single embolic infarct of the left supplementary motor area was characterized by initial mutism, rapid recovery to fluent speech marked by short sentences with normal grammar, persistent severe impairment of writing, and frustration and anxiety related to language tasks.