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Except for a handful of inherited cases related to known gene defects, Parkinson's disease (PD) is a sporadic neurodegenerative disease of unknown etiology. There is increasing evidence that inflammation and proliferation of microglia may contribute to the neuronal damage seen in the nigro-striatal dopaminergic system of PD patients. Microglia events that participate in neuronal injury include the release of pro-inflammatory and neurotoxic factors. Characterizing these factors may help to prevent the exacerbation of PD symptoms or to remediate the disease progression. In rodents, the nigro-striatal system exhibits high expression of the chemokine receptor CXCR4. Its natural ligand CXCL12 can promote neuronal apoptosis. Therefore, the present study investigated the expression of CXCR4 and CXCL12 in post-mortem brains of PD and control (non-PD) individuals and in an animal model of PD. In the human substantia nigra (SN), CXCR4 immunoreactivity was high in dopaminergic neurons. Interestingly, the SN of PD subjects exhibited higher expression of CXCR4 expression and CXCL12 than control subjects despite the loss of dopamine (DA) neurons. This effect was accompanied by an increase in activated microglia. However, results from post-mortem brains may not provide indication as to whether CXCL12/CXCR4 can cause the degeneration of DA neurons. To examine the role of these chemokines, we determined the levels of CXCL12 and CXCR4 in the SN of MPTP-treated mice. MPTP produced a time-dependent up-regulation of CXCR4 that preceded the loss of DA neurons. These results suggest that CXCL12/CXCR4 may participate in the etiology of PD and indicate a new possible target molecule for PD.

DeJong G, Horn SD, Conroy B, Nichols D, Healton EB. Opening the black box of post-stroke rehabilitation: stroke rehabilitation patients, processes, and outcomes. This article introduces the journal's supplement devoted to the methods and findings of the 7-site Post-Stroke Rehabilitation Outcomes Project (PSROP), a study designed to provide a very granular in-depth understanding of stroke rehabilitation practice and how practice is related to outcomes. The article summarizes current knowledge about the effectiveness of post-stroke rehabilitation, outlines where the PSROP fits into the broader traditions of stroke rehabilitation outcomes research, underscores the study's methodologic innovations, and summarizes the scope of the articles that follow.

Clinical services must monitor hospital-acquired morbidity, but what rates are expected specifically for neurology inpatients is not evident from published studies. We studied prospectively 1317 consecutive admissions to a neurology service in a university-affiliated city hospital from 1987 to 1990 and recorded all nosocomial infections, nosocomial pneumonia, and decubitus ulcers of stage III or IV. Over the 3-year period, 6.8% of patients had > or = 1 nosocomial infection (and almost half of these had a nosocomial bloodstream infection); 3.1% had > or = 1 case of nosocomial pneumonia; 1.2% developed severe decubitus ulcers, and 8.4% had one or more of the three complications. The incidence of nosocomial infection exceeds that expected from multihospital studies. How much of the excess is peculiar to neurology patients and how much can be attributed to factors in our community and at our hospital cannot be determined from this study. Furthermore, our statistics are not meant as norms, but as initial estimates for quality assurance.

We reviewed 153 episodes of cobalamin deficiency involving the nervous system that occurred in 143 patients seen over a recent 17-year period at 2 New York City hospitals. Pernicious anemia was the most common underlying cause of the deficiency. Neurologic complaints, most commonly paresthesias or ataxia, were the first symptoms of Cbl deficiency in most episodes. The median duration of symptoms before diagnosis and treatment with vitamin B12 was 4 months, although long delays in diagnosis occurred in some patients. Diminished vibratory sensation and proprioception in the lower extremities were the most common objective findings. A wide variety of neurologic symptoms and signs were encountered, however, including ataxia, loss of cutaneous sensation, muscle weakness, diminished or hyperactive reflexes, spasticity, urinary or fecal incontinence, orthostatic hypotension, loss of vision, dementia, psychoses, and disturbances of mood. Multiple neurologic syndromes were often seen in a single patient. In 42 (27.4%) of the 153 episodes, the hematocrit was normal, and in 31 (23.0%), the mean corpuscular volume was normal. Neutropenia and thrombocytopenia were unusual even in anemic patients. In nonanemic patients in whom diagnosis was delayed, neurologic progression frequently occurred although the hematocrit remained normal. In 27 episodes, the serum cobalamin concentration was only moderately decreased (in the range of 100-200 pg/ml) and in 2 the serum level was normal. Neurologic impairment, as assessed by a quantitative severity score, was judged to be mild in 99 episodes, moderate in 39 and severe in 15. Severity of neurologic dysfunction before treatment was clearly related to the duration of symptoms prior to diagnosis. In addition, the hematocrit correlated significantly with severity, independent of the longer duration of symptoms in nonanemic patients. Four patients experienced transient neurologic exacerbations soon after beginning treatment with cyanocobalamin, with subsequent recovery. Followup evaluation was adequate to assess the neurologic response to vitamin B12 therapy in 121 episodes. All patients responded, and in 57 (47.1%), recovery was complete, with no remaining symptoms or findings on examination. The severity score was reduced by 50% or greater after treatment in 91% of the episodes. Residual long-term moderate or severe neurologic disability was noted following only 7 (6.3%) episodes. The extent of neurologic involvement after treatment was strongly related to that before therapy as well as to the duration of symptoms. The percent improvement over baseline neurologic status after treatment was inversely related to duration of symptoms and hematocrit. Some evidence of response was always seen during the first 3 months of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

We wrote a list of descriptive phrases to dichotomize admissions to a neurology service by a priori perceptions of risk of death within 30 days as "higher than average" versus "lower than average." In 500 consecutive admissions, the higher-risk list carried a 17-fold relative risk of death for the 20% of admissions so classified. The list is a valid and informative predictor of 30-day outcome that supports a classification of deaths as "expected" or "unexpected."

Unilateral neglect is usually caused by lesions of the right cerebral cortex, especially parietal. Neglect after subcortical lesions has been reported rarely in thalamic or striatal hemorrhage, and after infarction of thalamus or striatum and internal capsule shown by CT. In these patients, there may have been compression or ischemia of overlying cerebral cortex and white matter. We report a patient with sensory hemineglect, asomatognosia, and anosognosia caused by infarction of striatum and deep white matter, with involvement of neither cortex nor thalamus and without mass effect. This is the first autopsy-confirmed example of human neglect with involvement of only the striatum and deep white matter.

Autosomal dominant motor system degeneration (ADMSD) is a hereditary ataxia that has been reported previously only in Portuguese families from the Azores Islands. Cerebellar ataxia, pyramidal and extrapyramidal signs, amyotrophy, dystonia, abnormal eye movements, and prominent eyes are variably present. Four members of a family had cerebellar ataxia, dystonic posturing, a variety of abnormal eye movements, and prominent eyes resulting from lid retraction. Eight other family members had a similar disease. The combination of cerebellar ataxia, dystonia, abnormal eye movements, and prominent eyes has been reported only in ADMSD. The family reported here may be the first example of ADMSD in a non-Portuguese family.

Benign intracranial hypertension (BIH) and empty sella syndrome occurred in a patient with Cushing syndrome resulting from adrenal adenoma, removal of which was followed by return of cerebrospinal fluid pressure to normal. This case does not clarify the pathophysiology of BIH, but it does raise questions about the treatment of BIH with corticosteroids, which are of unproved efficacy and may sometimes cause the same clinical syndrome.

A woman with typical symptoms of lithium toxicity had, in addition, severe generalized sensorimotor peripheral neuropathy, which cleared completely as the recovered. Electrodiagnostic studies suggested axonal lesions; autopsy ten months later revealed no residual abnormalities. Previous studies have shown that lithium can affect peripheral nerve function, but this is the first reported case of peripheral neuropathy in association with lithium toxicity.

In a prospective study, 34 patients with 41 admissions for malignant hypertension were examined by a neurologist before and after antihypertensive treatment. Neurologic examination was normal in 17 cases, and neurologic diagnoses in 19 others included acute cerebral infarction (10), uremic encephalopathy (4), dementia of uncertain etiology (3), multiple infarct dementia (1), and chronic paranoid schizophrenia (1). Five patients had a generalized neurologic syndrome consistent with hypertensive encephalopathy, characterized by altered mental function with or without generalized convulsions. In these patients, neurologic examination was normal 1 to 7 days after lowering of blood pressure, while renal function remained unchanged. Neurologic disease is therefore common in malignant hypertension, and hypertensive encephalopathy may be more frequent than previously described.

Acute global aphasia without hemiparesis has been considered pathognomonic of embolic stroke. During 1 year, we encountered six patients with this syndrome. Two had multiple strokes, probably embolic. One had atrial fibrillation; at autopsy, there were metastases as well as multiple infarcts in the left hemisphere. One had a single large infarct in the territory of an anterior branch of the middle cerebral artery (MCA), one had subarachnoid hemorrhage of unknown origin, and one had a sylvian fissure hematoma with intraparenchymal extension from a ruptured MCA aneurysm. Nonembolic etiologies are therefore also possible and include conditions that bar anticoagulation.

Cerebral sarcoidosis was found at autography in a 68-year-old woman with progressive dementia. Of 35 previously reported cases of central nervous system sarcoidosis with dementia, only 1 was over 65 years old, and in only 2 was the presenting clinical syndrome that of a degenerative dementia. Other unusual features of the index case include the restriction of the initial cognitive deficit to memory loss and mild anomia, the scarcity of antemortem evidence for systemic sarcoidosis, a positive tuberculin test, a cerebrospinal fluid (CSF) protein concentration as high as 2028 mg per deciliter. sarcoidosis is a rare but potentially treatable cause of dementia. Consistently normal CSF probably excludes the diagnosis.

Harlem Hospital Center lacks computed tomography (CT) facilities. During 1979 it attempted to share the CT facilities of two other institutions. Retrospective analysis reveals that under this arrangement only a small percentage of Harlem patients needing CT obtained it. Among patients recommended for CT, 252 of 1528 without trauma and six of 342 with trauma received it. In some instances there were difficulties in moving patients between hospitals. If transportation had been optimal, however, the other hospitals, because of their own needs, would have been unable to provide Harlem Hospital with more than a third of the CT scans requested. Furthermore, even if unlimited opportunities for scanning had been available, patients whose need for CT seemed most urgent--the very ill--would have been unable to receive it; of 163 patients who died without receiving CT as recommended, 93 were too sick or deteriorating too rapidly to be moved to the CT facilities. We conclude that CT cannot be effectively shared by large acute-care hospitals.

Since the introduction of computed tomography (CT), there have been numerous reports of brain abscess treated successfully without surgery. Because pathologic confirmation was lacking in these patients, diagnosis was based on CT abnormalities, usually ring enhancement. However, our recent clinical experience and the experimental work of others indicate that the "ring sign" on contrast-enhanced CT is not absolutely diagnostic of encapsulated brain abscess. Moreover, in the reported cases of alleged brain abscess cured medically, atypical clinical features suggest that some patients may have had cerebral infarction or cerebritis. Stricter clinical and radiologic criteria are needed before concluding that encapsulated brain abscess can be cured by medical therapy alone.

A 65-year-old man had four drop attacks in several days and then a fixed stroke with quadriplegia. At autopsy infarction in the lower pons and upper medulla affected principally the corticospinal tracts. Tegmental destruction included reticular formation nuclei with rostral projections, but spared the lateral reticular formation nuclei, from which arise the descending reticulospinal tracts. This case is the first detailed autopsy report of a patient with drop attacks, and supports the view that at least some drop attacks are caused by transient ischemia of the corticospinal tracts.

A patient is reported in whom a subdural sarcoid granuloma caused symptoms of an intracranial mass lesion, and disappeared following steroid therapy. Twenty-three previous cases with large intracranial sarcoid granulomas have been documented, a review of these 24 cases leads the authors to conclude that: 1) neither symptoms nor nonhistological diagnostic studies, including computerized tomography, differentiate sarcoid from cerebral neoplasms or other central nervous granulomas; and 2) because sarcoid mass lesions frequently respond well to corticosteroid therapy, surgery should probably be reserved for cases in which there is diagnostic uncertainty, a need for emergency decompression, or lack of response to steroids.

A right-handed woman developed left hemiparesis and a language disturbance. At autopsy, there was infarction in the territory of the right anterior cerebral artery, involving, among other structures, the supplementary motor area. This brain region has been considered to play a role in speech, but whether the language disorder that follows its destruction is truly aphasic is controversial. Our patient does not answer that question, but if her disturbed language is viewed as aphasic, she represents the fourth autopsy case of "crossed aphasia in a dextral" and the first, with or without autopsy, after right anterior cerebral artery occlusion.

Among 141 consecutive patients with neuro-psychiatric abnormalities due to cobalamin deficiency, we found that 40 (28 percent) had no anemia or macrocytosis. The hematocrit was normal in 34, the mean cell volume was normal in 25, and both tests were normal in 19. Characteristic features in such patients included paresthesia, sensory loss, ataxia, dementia, and psychiatric disorders; longstanding neurologic symptoms without anemia; normal white-cell and platelet counts and serum bilirubin and lactate dehydrogenase levels; and markedly elevated serum concentrations of methylmalonic acid and total homocysteine. Serum cobalamin levels were above 150 pmol per liter (200 pg per milliliter) in 2 patients, between 75 and 150 pmol per liter (100 and 200 pg per milliliter) in 16, and below 75 pmol per liter (100 pg per milliliter) in only 22. Except for one patient who died during the first week of treatment, every patient in this group benefited from cobalamin therapy. Responses included improvement in neuropsychiatric abnormalities (39 of 39), improvement (often within the normal range) in one or more hematologic findings (36 of 39), and a decrease of more than 50 percent in levels of serum methylmalonic acid, total homocysteine, or both (31 of 31). We conclude that neuropsychiatric disorders due to cobalamin deficiency occur commonly in the absence of anemia or an elevated mean cell volume and that measurements of serum methylmalonic acid and total homocysteine both before and after treatment are useful in the diagnosis of these patients.