Hepatocyte growth factor in cerebrospinal fluid in neurologic disease.

OBJECTIVE: To investigate hepatocyte growth factor (HGF) concentration in cerebrospinal fluid (CSF) in neurologic disease. MATERIALS AND METHODS: We determined CSF concentration of HGF with human-HGF-specific enzyme-linked immunosorbent assays (ELISA) in 121 patients: Alzheimer's disease (AD) (33), amyotrophic lateral sclerosis (ALS) (10), Parkinson's disease (PD) (5), progressive supranuclear palsy (PSP) (3), spinocerebellar degeneration (7), acute disseminating encephalomyelitis (ADEM) (6), human T-lymphotropic virus-1 (HTLV-1)-associated myelopathy (HAM) (6), multiple sclerosis (MS) (7), aseptic meningitis (AM) (12), and peripheral neuropathy and myopathy as control diseases (32). RESULTS: HGF concentrations in CSF were significantly higher with diseases of the central nervous system (CNS) than control diseases and were slightly higher with AD than other neurodegenerative diseases. Values were highest with ADEM but decreased during corticosteroid treatment. We found no relationship between HGF in CSF and CSF cells or protein, immunoglobulin index, or Q albumin. CONCLUSION: It is suggested that high concentrations of HGF in CSF may be partially related to CNS pathology, especially to demyelinating disease.

A case of Isaacs syndrome with high CSF protein and a large cisterna magna.

An 11-year-old boy exhibited continuous muscle fiber activity. He had suffered from stiffness of his hands, difficulty in relaxing his hands after gripping, and making skilled movements with his fingers. His clinical symptoms improved after treatment with carbamazepine. Electromyography (EMG) showed that he had continuous electrical discharges both at rest and during sleep. These discharges completely disappeared after the peripheral nerve was blocked with Lidocaine. An evoked electromyogram showed suppression of abnormal discharges after the F response. These electrophysiological findings indicated that the disorder originated in the spinal anterior horn cells. CT scanning showed a large cisterna magna in the posterior cranial fossa. Protein in the cerebrospinal fluid was elevated.

Peripheral neuropathy associated with eosinophilia-myalgia syndrome.

In 1989, the Centers for Disease Control recognized the existence of an epidemic illness characterized by myalgia and eosinophilia in individuals taking preparations containing L-tryptophan. We evaluated 3 patients with eosinophilia-myalgia syndrome who presented with subacute progressive neuropathies. The neuropathies were predominantly motor and maximal in the lower extremities. Two patients were confined to a wheelchair and one was ventilator-dependent and bedridden. Sensory loss predominantly involved small fiber modalities. Electrophysiological studies showed multifocal marked conduction slowing and conduction block indicating segmental demyelination, with associated axonal degeneration that was accentuated distally. Examination of sural nerve biopsy specimens demonstrated axonal degeneration in all 3 patients and perivascular infiltrates in 2. Levels of quinolinic acid, a neurotoxic metabolite of L-tryptophan, were elevated in the cerebrospinal fluid in the 2 patients in whom it was measured. The cause of the neuropathy is unknown but may include immune mechanisms or toxicity of eosinophils, L-tryptophan, its metabolic products, or contaminants within L-tryptophan preparations.

Norepinephrine and gamma-aminobutyric acid in amyotrophic lateral sclerosis.

Patients with amyotrophic lateral sclerosis have increased levels of the neutrotransmitter norepinephrine in blood and cerebrospinal fluid and depressed levels of the inhibitory neurotransmitter gamma-aminobutyric acid in cerebrospinal fluid. These neurochemical alterations are most marked in patients bedridden with advanced disease, appear interrelated, and lead to cardiovascular alterations in patients with amyotrophic lateral sclerosis.

Relationship between cerebrospinal fluid norepinephrine and blood pressure in neurologic patients.

In 126 patients hospitalized for various diseases norepinephrine in cerebrospinal fluid correlated with blood pressure (r = 0.41, p < 0.0001). Plasma and cerebrospinal fluid norepinephrine levels correlated with heart rate. Central noradrenergic nerves help control blood pressure and may be involved in human hypertension.

Chronic progressive myelopathy: investigation with CSF electrophoresis, evoked potentials, and CT scan.

Chronic progressive myelopathy (CPM) is a difficult clinical problem. Many patients who present with CPM turn out to have a spinal form of multiple sclerosis (MS), but until there is clear lesion dissemination, a definite clinical diagnosis cannot be made. We have looked for MS-related abnormalities in 72 patients with CPM. The mean age of onset was 42 years, mean duration was ten years, and mean Kurtzke disability rating was 4.5. Studies performed were cerebrospinal fluid electrophoresis for oligoclonal banding, pattern-reversal visual evoked responses, blink reflex latencies, and computerized axial tomography. Oligoclonal banding was found in 32 patients (44%), patterned visual evoked responses were abnormal in 32 (44%), and blink latencies were abnormal in 40 (56%). A least one of these studies was abnormal in 61 patients (85%) and at least two in 48 (66%). The CT scan was abnormal in 38 )53%), 36 with atrophy and 3 with low-density or enhancing lesions. These results suggest that at least 44% of patients with CPM may have MS that could be diagnosed by oligoclonal bands. Other physiological tests suggesting diffuse or disseminated disease bring the total to 85%. Only autopsy follow-up will tell us the exact diagnostic accuracy of these studies in this complex syndrome.