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Paraneoplastic neurologic syndromes are degenerative diseases of the central or peripheral nervous system that develop in association with a systemic neoplasm without a direct invasion by tumor. The pathogenesis of this disorder has been hypothesized in the past, and now there is increasing evidence that autoimmune processes triggered by the underlying neoplasm play a major role in the pathophysiology, as documented by many reports of identification of autoantibodies that react with both the target neural tissue and the underlying neoplasm, as evidenced by the extensive application of molecular biology techniques. The presence of antibodies in serum or CSF of some patients with this disorder now accurately identifies the subgroup of the disorders related to specific neoplasms. The trend of recent studies on the pathogenesis of this disease may in the future lead to a new era to clarify the pathogenesis.

A hippocampal 38 kd autoantigen recognized by an autoantibody from the serum of a patient with paraneoplastic limbic encephalitis (PLE) and small cell lung carcinoma (SCLC) was isolated by screening a human hippocampal cDNA library. The 1,991-nucleotide ple21 clone was obtained and the deduced 350-residue protein encoded by the ple21 cDNA clone was found to be highly homologous to the neuron-specific RNA recognition motifs (RRMs)-containing proteins. The homologies were confined to the RRMs and the RRM connecting region. The presence of RRM in the antigenic protein may be important in the pathogenesis of SCLC-associated paraneoplastic neurologic syndrome.

We examined the expression of the paraneoplastic cerebellar degeneration-associated autoantigen (PCD-AA) protein in human tumor lines of different origins by using an immunoaffinity-purified antibody from a patient with paraneoplastic cerebellar degeneration (PCD) and uterine adenocarcinoma. Immunocytochemical studies revealed that this antigen is expressed in the cytoplasm of two different uterine carcinoma lines and the tumor lines of neural origin as well as in the cytoplasm of a normal skin fibroblast line. By immunoblot analysis, we detected a 52-kd antigen identical to the PCD-AA protein in all the cell lines studied, including a colon adenocarcinoma line, a small-cell lung carcinoma line, and a squamous cell lung carcinoma line. These results indicate that the PCD-AA protein is expressed in a wide range of tumor cells. In this respect, this antigen is distinguishable from the cerebellar degeneration-related-34 antigen, of which expression is confined to tumor lines of neuroectodermal origin and not detected in colon, breast, or ovarian carcinoma lines derived from patients without PCD. These findings suggest the variability of the immune response to antigens in PCD.

We describe an electro-oculographic study of upbeat nystagmus in 4 patients, with neuropathological correlation in one. All patients had lesions in the pontine tegmentum. The electro-oculographic data may be explained by imbalanced vertical vestibular or smooth pursuit eye movement control. The nystagmus stopped or reversed direction during convergence or in supine head positions. We propose that changes in the intensity or direction of upbeat nystagmus that are induced by convergence or changes in head position, are caused by vertical imbalance in the otolithic-ocular reflex, when superimposed on an imbalanced vestibulo-ocular reflex (VOR). Imbalance of the otolithic-ocular reflex and the vertical VOR are caused by damage in the pontomedullary tegmentum.

A 13-year-old boy was the victim of attempted strangulation. His condition had returned to normal by the sixth day after the assault; however, from the seventh day, choreoathetosis, dystonia, and marked pseudobulbar paralysis developed in the boy. The computed tomographic scans and T2-weighted magnetic resonance images that were obtained at this time revealed low-density and high-signal intensities in the region of the bilateral putamen and caudate nucleus. These symptoms and the changes in his computed tomographic scans and magnetic resonance images subsided gradually during a 2-month period. Sequential analysis of the cerebrospinal fluid for gamma-aminobutyric acid and dopamine concentrations during his illness revealed reciprocal changes with normal recovery. Because of the delayed onset of neurological changes and the cerebrospinal fluid showing reversible symptoms, the delayed encephalopathy after strangulation had been related to the biochemical alterations that followed anoxia in the vulnerable basal ganglia.

We report an electro-oculographic study (EOG) of upbeat nystagmus and neuroradiological correlations in 4 patients and neuropathological findings in 1 patient. All 4 patients revealed responsible lesions in the lower pontine tegmentum. The EOG data suggest that our patients had a deficit in vertical smooth eye movement balance. The nystagmus stopped or reversed direction during convergence or changes of head position. These EOG findings might be caused by vertical imbalance in the otolithic ocular reflex, superimposed on an imbalanced vestibulo-ocular reflex (VOR), secondary to a damage to the pontomedullary tegmentum.

Acute effects of various anticonvulsants on brain-stem auditory evoked potentials (BAEPs) in rats were tested. A high dose of phenytoin abolished all BAEP waves. Carbamazepine increased all 4 wave latencies. Phenobarbital and clonazepam increased the latencies of waves IV and III. Therefore, if BAEPs are to be used as an ancillary test for brain death, the possibility of significant effects of high dosages of anticonvulsants on BAEPs must be considered.

Objective To report a case of familial amyloid polyneuropathy homozygous for the amyloidogenic transthyretin (ATTR) Val30Met gene with motor-dominant sensorimotor polyneuropathy and unusual sural nerve pathological findings. Methods Mass spectrometry analysis and polymerase chain reaction–restricting fragment length polymorphism were performed. A right sural nerve biopsy specimen was obtained for histological investigation. Setting Academic medical center. Results A 56-year-old Japanese man living in a local town (Nakajima, Japan) in Ishikawa Prefecture, a nonendemic area of type I familial amyloidotic polyneuropathy, had vitreous amyloidosis, motor-dominant sensorimotor polyneuropathy, erectile dysfunction, and urinary incontinence. He had neither orthostatic hypotension nor indolent diarrhea. Restriction enzyme analysis with Eco T22 I of amplified DNA and mass spectrometry analysis revealed homozygosity for ATTR Val30Met . Of 8 family members, 5 were evaluated and found to be heterozygous for ATTR Val30Met ; a family history found no relative with the similar neurologic disorders. The sural nerve biopsy specimen showed focal edema and an amyloid deposit in the subperineural tissue, associated with moderate loss of myelinated and unmyelinated fibers. Conclusions In addition to the findings characteristic of homozygosity for ATTR Val30Met such as vitreous amyloidosis and relatively less autonomic involvements, this case had the unique findings of motor-dominant sensorimotor polyneuropathy and unusual sural nerve biopsy specimen results.

Microchemical techniques correlated with histologic observations in adult rat optic nerve were used to study the response of neuroglia to progressive membranous destruction of myelinated axons between 1 and 200 days after surgical removal of the eye. Cell enumeration was accomplished by combining DNA assays with differential cell counts in electron microscopic montages previously reported by others. During the first week after nerve transection, ganglioside sialic acid and proteolipid proteins decreased by 57% and 28%, respectively; these changes preceded the subsequent reduction of cerebrosides and cholesterol and light microscopic evidence of myelin destruction. This suggests that degeneration of axon cylinders and degradation of the protein core of myelin may be initiating events which induce instability in the lipid structure and subsequent fragmentation of the sheath. Transformation of astrocytes into undifferentiated glia with high ribosomal content also occurs during the initial phase of axonal degeneration, yielding a new line of cells capable of engulfing and digesting membranous debris. The slow clearance of degenerating fibers at about one-third the rate reported for peripheral nerve may be explained by the lack of infiltration of macrophages from blood and the relatively limited capacity of undifferentiated glia for phagocytosis.

Nerve conduction velocity (NCV) measurements have been widely used to assess the electrophysiological properties of peripheral nerves and to detect neuropathies at a subclinical stage. Conventional NCVs are usually expressed as the NCV for the fastest conducting fibers and the current standard methods do neither supply information about slower conducting fibers, nor detect information about individual fiber groups. We present a new analytical method, to estimate the distribution of conduction velocity (DCV), based upon spectral analysis of the wave forms of two compound action potentials (CAPs) recorded by surface electrodes from a nerve bundle. If the spectra of the two CAPs recorded at two different sites in response to supramaximal electrical stimulation at distances l1 and l2 are given as G11(omega) and G12(omega), the spectral representation of the latency distribution P12(omega) for the propagation distance l2 is expressed as follows: P12(l1 omega/l2) = [G11(omega)/G12(omega)]P12(omega), where omega is an angular frequency. We developed an algorithm that computes P12(omega) successively without using iterative calculation methods. Our estimation method is theoretically based upon the principle that the CAPs are recorded monopolarly to estimate the DCV, but in practical use, it is almost impossible to obtain appropriate CAP wave forms by monopolar recording methods, because of stimulation and muscle artefacts. In order to evaluate the efficacy of bipolarly recorded CAP wave forms for this computation algorithm, we examined the two CAP wave forms reconstructed by simulation techniques. We found that the difference between the monopolar and bipolar recording methods was reflected in the wave form extracted for the single fiber action potentials but not in the latency distribution. The distance between the bipolarly recorded electrodes (1.5 cm was the minimal distance used) did not affect the reproducibility of estimating the latency distribution. This new method is non-invasive and could be used for evaluation of peripheral neuropathies.

Electrolyte-induced myelinolysis was produced in rats to evaluate electrophysiological derangement in the brainstem. Auditory brainstem responses (ABRs) were used to assess the brainstem function. Rats treated with hypertonic saline for 2 days had normal interpeak latencies in ABRs. Rats treated with vasopressin-induced hyponatremia alone and those with hypertonic saline after 3 days of hyponatremia had significantly prolonged interpeak latencies between waves II–III and III–IV in ABRs. These prolongations indicate electrophysiological derangement of the upper pons and mesencephalon in hyponatremic rats as well as in rats with hyponatremia followed by hypernatremic myelinolysis. In view of these data, hyponatremia may be a prerequisite for electrolyte-induced myelinolysis and electrolyte derangements such as hyponatremia, and rapidly correcting hypernatremia may be the cause of electrolyte-induced myelinolysis in rats.

A case of Fabry's with pulmonary regurgitation is reported, and the cause of valvular involvement, the electrophysiological mechanism of the short PR interval, and the usefulness of the endomyocardial biopsy method in an attempt to establish the diagnosis in Fabry's disease have been discussed.

✓ The authors present 19 cases of cervical spondylotic myelopathy in patients with developmentally narrow canal treated by microsurgical anterior osteophytectomy with interbody fusion, with follow-up periods of 1 to 8 years (mean 38 months). Postoperatively, the lower limb function, evaluated by Nurick's six-grade classification, improved two or three grades in 16 cases, one grade in two cases, and remained unchanged in one case. The upper limb function, evaluated by the authors' own four-grade classification, improved two or three grades in 11 cases, one grade in seven cases, and remained unchanged in one case. No deterioration caused by the osteophytectomy was seen. During the follow-up period, spondylolisthesis appeared 31 months postoperatively in one patient and soft disc hernia occurred 66 months postoperatively in another; these two patients were treated by a second operation and cervical traction, respectively. The authors conclude that anterior osteophytectomy with interbody fusion is applicable as a surgical treatment of cervical spondylotic myelopathy even where developmental canal stenosis is present.

Brain stem type neuro-Behçet's syndrome was studied with enhanced CT and MRI during the acute and chronic stage of the illness. During the acute stage, brain CT revealed a low density lesion in the brain stem extending from the lower pons up to the midbrain ventrolaterally with marginal enhancement effect. T2-weighted image showed a high signal intensity lesion in the brain stem which mainly involved the basis ponti, tegmentum, tectum and cerebral peduncle. During the chronic stage, the lesion became low in signal intensity with T2-weighted image and reduced in its size without enhancement in brain CT. The prolonged relaxation time of the lesions was gradually normalized with steroid treatment. Sequential brain CT with enhancement and MRI study with T1- and T2-weighted images were useful to detect the lesions and to evaluate the activity in the neuro-Behçet's syndrome.

Operative results of microsurgical anterior discectomy for cervical spondylotic radiculomyelopathy are reported. Anterior discectomy was carried out using Smith & Robinson's method under an operating microscope and all compressive components against the spinal cord and the radicula, such as degenerated disks, osteophytes, barridges and calcified ligaments, were completely removed using curettes and air-drills. Uncectomy was also performed whenever necessary to relieve the radicular compression. A total of 38 patients, 24 males and 14 females, on whom conservative treatment had not been effective, underwent surgery. Myelopathy was present in all 38 patients, and among these moderate weakness of the lower extremities and spastic gait were seen in 19 patients (50%), and severe paraparesis including a bed-ridden state were noted in 9 patients (24%). Neurogenic bladders were observed in 13 patients (34%). Radiculopathy was also present in 20 patients. In roentgenograms, sagittal A-P diameter of the cervical vertebral canal at C5 ranged between 16.4 mm and 10.4 mm (mean 13.5±1.6), and developmental narrow canals with a value of less than 12.0 mm were noticed in 9 patients. Discectomy at a single level was performed on 22 patients, two levels on 14 and three levels on 3. There was a total of fifty-six discectomies. Fortyseven spaces were fused by autogenous iliac bone grafts and nine were without grafts. Follow up results over 6 months were evaluated on 36 patients (average observation period: 20 months) according to a modified Odom's scale. Twenty patients were judged as excellent, ten good and six fair. As a result 30 out of 36 cases (83%) regained full daily activity with minimum disabilities. Radiculopathy was relieved in 19 patients (95%). Neurogenic bladder disappeared in all 13 patients. There was no operative deterioration. Ages over 60 years old and preoperative periods of over a year were considered as factors deferring postoperative recovery. Severe myelopathy showing a transverse syndrome was also a poor prognostic factor, but all four of the bed-ridden patients became ambulatory. In summary, total removal of the compressing components of cervical spondylosis under a microscope proved to be warrantted treatment for both myelopathy and radiculopathy.

The acute onset of symptoms of severe cervical radiculo-myelopathy in four patients with athetoid-dystonic cerebral palsy is reported. Neurological and radiological examination showed that the spondylotic changes of the cervical spine were responsible for new neurological deficits leading to the patients being bedridden. Dystonic-athetoid neck movements may cause excessive axial neck rotation as well as flexion and extension movements of the spine. These repetitive exaggerated movements may result in early degenerative changes of the vertebrae which may enhance the radiculo-myelopathy. The four patients were treated with an anterior discectomy with interbody fusion. They were bedridden pre-operatively but all have since been able to walk with or without a cane. It is concluded that early anterior decompression with interbody fusion is a treatment of choice for cervical spondylotic radiculo-myelopathy in association with athetoid cerebral palsy.

Characteristic movement disorders were observed in two siblings who had neuroacanthocytosis syndrome with normal serum lipoprotein levels. The disorders included orolingual tic-like movements associated with vocalization, biting of the lip and tongue, peculiar dysphagia with bird-like drinking, and postural lapse with abrupt buckling of the knees. In addition, subtle features of parkinsonism and chorea were observed. These movement problems are strikingly similar to those described in cases of neuroacanthocytosis syndrome in several other familial and sporadic cases. Careful observations of these unusual movement disorders may provide a clue to the diagnosis of this rare syndrome.

Microchemical techniques correlated with histologic observations were used to study rat optic nerve at 5, 10, 15, 20, 30, 40 and 50 days of postnatal development. Cell enumeration was accomplished by combining DNA as says with previously reported differential cell counts in electron microscopic montages (Vaughn, '69). At 5 days of age, the optic nerve contained unmyelinated axons, and its volume and total number of glia (DNA) were less than 40% of 50-day-old values. The cell population was composed of equal numbers of fibrous astrocytes and glial stem cells but contained only 7% oligodendrocytes. Between 5 and 20 postnatal days, mitotic proliferation of these stem cells resulted in a 3-fold increase of DNA, while numbers of oligodendroglia increased 10-fold. The cell population of the nerve at 20 postnatal days was similar to that found in the adult, with oligodendrocytes constituting 60% of the total cell population. Although these cells continuously formed myelin throughout postnatal development, their maximal rate of myelin lipid deposition (cerebrosides and cholesterol) occurred between 5 and 20 postnatal days. Hence, the most rapid rate of myelinogenesis in rat optic nerve occurred during the first three weeks of postnatal life and was synchronous with the mitotic proliferation and cellular differentiation of interfascicular oligodendroglia.

✓ A 57-year-old man presented with a pulmonary mass and subacute onset of paraplegia. Laboratory examination revealed an increased protein content in the cerebrospinal fluid and a normal myelogram. Autopsy disclosed epidermoid carcinoma in the left lower lobe of the lung, intramedullary metastasis at the midthoracic level, and a central pencil-shaped softening above and below the metastatic lesion. The pencil-shaped softening was an ischemic infarct rather than of hemorrhagic or congestive origin. The pathogenesis of this rare association may be explained by the hypothesis of a tumor embolus in the arterial circulation that feeds the center of the cord, producing metastasis. This embolus was followed later by a second embolus to a radicular artery, causing the pencil-shaped softening of the spinal cord.

In six patients with CT evidence of posterior thalamic hemorrhage, we found the following signs: saccadic hypometria away from the lesion; defective pursuit toward the lesion with corresponding opticokinetic abnormalities; mild ipsilateral ptosis; ipsilateral miosis; unilateral sensory neglect; and sensorimotor hemiparesis. This distinct syndrome has a benign course and satisfactory recovery. It differs from the classic picture of thalamic hemorrhage, and can be called "the syndrome of posterior thalamic hemorrhage."

An autopsy case of central pontine myelinolysis (CPM) was reported. The patient, a 48-year-old man, with a long history of alcoholic intake appeared in a hospital with the diagnosis of alcoholic hepatitis and the neurologic symptoms of delirium tremens. During the hospital course he fell into "locked in" with concomitant development of marked hyponatremia (92 mEq/1). An autopsy revealed typical CPM and the extra-pontine myelinolytic lesions distributed symmetrically in the thalami, subthalamic nuclei, and lateral geniculate bodies. Spongiosis was also found in the deep layer of the cerebral cortex and in the putamen. It was suggested that CPM occur in close association with marked hyponatremia and the extrapontine involvement be likely to manifest in the deep layer of the cerebral cortex, putamen, thalamus, and lateral geniculate body, where the myelin cylinders form an interlacing network embedding large neurons and oligodendrocytes.

We used mass fragmentography to analyze a very long-chain fatty acid composition of erythrocyte membrane sphingomyelin. The content of hexacosanoic acid (C26:0), tetracosanoic acid (C24:0) and docosanoic acid (C22:0) in adrenoleukodystrophy (ALD) hemizygotes and heterozygotes was significantly higher than in controls. Although the ratio of C26:0 to C22:0 in 18 of the 46 controls was in the range of ALD heterozygotes, the absolute content of C26:0 and C24:0 in controls did not overlap with ALD hemizygotes or heterozygotes. The content of C26:0 and C24:0 is more reliable for detection of ALD hemizygotes and heterozygotes than the ratio of C26:0 to C22:0 when red cell sphingomyelin is used for diagnosis.

This study reports a case of MELAS with epileptic seizure, and reviews the characteristics of seizures in patients with this syndrome. They are characterized by: (1) generalized and/or partial seizures, (2) frequent association with visual symptoms and hemiparesis, and (3) posteriorly predominant EEG abnormalities.

• A 62-year-old man had an acute, transient, flaccid paraplegia. Examination showed a primary cardiac tumor with emboli to major branches of the aorta. A myxoma was removed from the left atrium, and normal function returned. Left atrial myxoma should be suspected as a cause for embolism to the CNS.

In a patient with phenytoin (PHE) intoxication, the brainstem auditory evoked potentials (BAEPs) were lost except for wave I and wave V. The patient recovered. In rats given PHE, we found changes in amplitude, morphology, and latency of BAEP. Within 5 minutes, all waves disappeared except for wave I, and soon thereafter all waves were lost, with PHE plasma concentration between 45.8 and 52.1 micrograms/ml or above. Ninety minutes after infusion, waves gradually reappeared. Loss of BAEP cannot be used as a criterion for brain death unless PHE intoxication is ruled out.