[Hypertrophic cranial pachymeningitis as a rare cause of headache]. / Hypertrophe kraniale Pachymeningitis als seltene Ursache für Kopfschmerzen.

Hypertrophic cranial pachymeningitis is an uncommon, fibrosing, inflammatory process that involves the dura mater. The condition is being reported more frequently owing to the use of cranial MRI. The main clinical feature is headache, whereas cranial nerve lesions, cerebellar symptoms, and epileptic seizures occur more rarely. A variety of autoimmune and infectious diseases can result in this condition, which is labeled as idiopathic in the absence of any definite inciting factor. The diagnosis of hypertrophic cranial pachymeningitis is based on neuroimaging of thickened and enhancing dura mater. It can be defined pathologically on biopsy. A specific treatment is indicated in some cases of secondary hypertrophic cranial pachymeningitis. Mostly, treatment relies on corticosteroids and immunosuppressive agents. This review summarizes the current knowledge on causes, clinical presentation, diagnosis, and treatment of this disorder.

Differential somatic CAG repeat instability in variable brain cell lineage in dentatorubral pallidoluysian atrophy (DRPLA): a laser-captured microdissection (LCM)-based analysis.

Employing a laser-captured microdissection (LCM), we have investigated the somatic instability of CAG repeats in the variable brain cell lineage in three patients with dentatorubral pallidoluysian atrophy (DRPLA). LCM enables the isolation of single lineage brain cells for subsequent molecular analysis. We have found that CAG repeat size and the range of CAG repeats in the cerebellar granular cells is smaller than those in cerebellar glial cells. Similarly, those in the cerebral neuronal cells are significantly shorter than those in cerebral glial cells. These data directly indicate that the CAG repeat is relatively more stable in neuronal cells than in glial cells. Furthermore, cerebellar granular cells show significantly smaller main CAG repeat size and CAG repeat range than either Purkinje cells or cerebral neuronal cells, suggesting that somatic instability in the CAG repeat is markedly variable even among the different types of neuronal populations. The cell-specific CAG repeat instability may thus be more complex than has previously been considered. LCM is a powerful tool for elucidating the mechanism of the triplet repeat instability of each cell type.

Axonal and perikaryal involvement in chronic inflammatory demyelinating polyneuropathy.

OBJECTIVES: To assess the extent of loss of myelinated nerve fibres and spinal motor neuron loss in chronic inflammatory demyelinating polyneuropathy (CIDP), a clinicopathological study was conducted on biopsied sural nerves and necropsied spinal cords from patients with CIDP. METHODS: The myelinated fibre pathology of 71 biopsied sural nerves and motor neuron pathology of nine necropsied spinal cords at L4 levels in patients with CIDP were quantitatively and immunohistochemically assessed. RESULTS: Myelinated nerve fibre density was significantly diminished to 65.4% of the control values (p <0.0001), correlating inversely with the extent of segmental demyelination and remyelination (r = -0.43, p < 0.0005) and duration of illness (r = -0.31, p < 0.01). Numbers of large spinal motor neurons in CIDP were variably but significantly diminished (range from 46.0 to 97.6% of the age matched control value (p < 0.005)), and reactive astrogliosis was evident in the ventral horn in CIDP. The frequency of ventral horn neurons exhibiting central chromatolysis and the accumulation of phosphorylated high molecular weight neurofilament protein was significantly higher in CIDP than in controls (p<0.01 and p<0.05). CONCLUSIONS: The loss of nerve axons and spinal motor neurons is common in CIDP, and extensive in some cases. These neuronal and axonal losses may influence the functional prognosis in CIDP.

[A case of Satoyoshi syndrome with symptoms resembling neuroleptic malignant syndrome].

Satoyoshi syndrome is a rare neurological disorder of unknown etiology characterized by progressive muscle spasms, alopecia, diarrhea and skeletal abnormalities. We here describe a 25-year-old man who developed symptoms similar to neuroleptic malignant syndrome (NMS). He began to have the clinical characteristics of Satoyoshi syndrome at the age of 12 years. He was admitted to hospitals many times with painful muscle spasms and pyrexia in the early stage of the disease. He received steroid pulse therapy and oral prednisone at the age of 19, the extent and frequency of the spells being reduced thereafter. He was admitted to our hospital due to recurrence of his usual muscle spasms. He was treated with midazolam intravenously to relieve severe muscle ache, pain in the left shoulder, and insomnia. About 90 minutes later, he became comatose, with the following manifestations: hyperthermia, low blood pressure, tachycardia, profuse perspiration, acute respiratory failure, and ensuing cardiac arrest. He developed rhabdomyolysis, acute renal failure, hepatic damage, and diffuse intravascular coagulation. Serum creatine kinase level was elevated to 306,910 IU. He died of multiple organ failure 13 days after admission. His symptoms resembled NMS and malignant hyperthermia (MH). None of patients with Satoyoshi syndrome accompanied by NMS or MH have been reported. It remains to be clarified whether midazolam administration induces NMS in Satoyoshi syndrome. Nevertheless, careful attention should be paid when one administers midazolam to patients with this syndrome.

Somatic mosaicism of the expanded CAG trinucleotide repeat in mRNAs for the responsible gene of Machado-Joseph disease (MJD), dentatorubral-pallidoluysian atrophy (DRPLA), and spinal and bulbar muscular atrophy (SBMA).

The CAG trinucleotide repeats in mRNAs for the responsible genes of Machado-Joseph disease (MJD), dentatorubral-pallidoluysian atrophy (DRPLA), and X-linked spinal and bulbal muscular atrophy (SBMA) were examined in various neural and nonneural tissues of affected individuals. The tissue-specific variation of expanded CAG repeat alleles were apparent for mRNAs of all three genes. The expanded CAG repeats of the mRNA were shorter in the cerebellum than in other regions of the central nervous system in DRPLA and MJD, but not in SBMA, and were longer in the liver and colon in MJD. Transcripts of the responsible genes with expanded CAG repeats were detected in all tissues studied, and the tissue-specific variation in the CAG repeat size of the mRNA did not correlate with the tissue-specific severity of pathological involvement in these diseases.

Differential pattern in tissue-specific somatic mosaicism of expanded CAG trinucleotide repeats in dentatorubral-pallidoluysian atrophy, Machado-Joseph disease, and X-linked recessive spinal and bulbar muscular atrophy.

We investigated the somatic mosaicism of trinucleotide repeat expansion in the neural and nonneural tissues of a dentatorubral-pallidoluysian atrophy (DRPLA), Machado-Joseph disease (MJD), and spinal and bulbar muscular atrophy (SBMA) patient and their correlation to the topographical distribution of the pathological involvement. The spatial pattern of tissue-specific somatic mosaicism in the CAG repeat size was significantly different among the DRPLA, MJD and SBMA patients. The size of the major bands of the mutant CAG repeat allele was significantly smaller in the cerebellar cortex in both DRPLA and MJD patients by 6 and 2 repeat units respectively and larger in the colon and liver of DRPLA by 5 repeats or more. There were also 1-2 repeat-sized small variations of major band size among the neural tissues in DRPLA. In contrast, there was no tissue-specific variation of major bands of CAG repeats and diversity of extra bands among the examined tissues including the cerebellum in the SBMA patient. There was no parallel occurrence of tissue-specific CAG instability and severity of neuropathological involvement in the neural and nonneural tissues of DRPLA, MJD and SBMA patients. Lack of significant tissue-specific somatic mosaicism in SBMA including the cerebellar cortex may suggest that CAG repeat expansion in the mutant androgen receptor gene is far more stable compared with that in DRPLA and MJD as well as those reported in Huntington's disease.

[Multiple system atrophy (MSA)].

The clinical and pathological features of 47 cases of multiple system atrophy (MSA) were analyzed. The mean age of onset was 56.7 (range 40 to approximately 76) years and mean survival was 5.7 (range 1.5 to approximately 12) years. Parkinsonism occurred in 31 cases. Helpful early points to the diagnosis included rigid-akinetic type, rapid progression, failure to respond to L-DOPA and other signs such as autoromic dysfunction, cerebellar ataxia and pyramidal signs, but these were not always present. T2 weighted MR images demonstrated decreased signal in the putamen and/or slit-hyperintensity in the outer margin of the putamen. These clinical and MRI findings are useful in the differential diagnosis between Parkinson's disease and MSA. Glial cytoplasmic inclusions (GCIs) were found in all 21 cases, but not in control brains. Several types of neuroral inclusion were also observed; large neuroral cytoplasmic, small neuroral cytoplasmic and nuclear inclusions. GCIs were labeled by antiubiquitin, anti-alpha and beta-tubulin and antitau antibodies. Large neuronal cytoplasmic inclusions (NCIs) observed in the pontine nuclei were positive with only antiubiquitin antibody.

Cerebrospinal fluid levels of superoxide dismutases in neurological diseases detected by sensitive enzyme immunoassays.

We measured cerebrospinal fluid (CSF) levels of Cu/Zn superoxide dismutase (Cu/Zn SOD) and Mn superoxide dismutase (Mn SOD) using enzyme immunoassays in 196 neurological patients and 44 controls. The mean Cu/Zn SOD level was 55.8 +/- 27.6 (SD) ng/ml and the Mn SOD, 8.0 +/- 2.5 ng/ml in the controls. Cu/Zn SOD or Mn SOD levels showed neither age-nor sex-related differences in the controls. Both SODs were markedly elevated in cerebrovascular diseases, bacterial meningitis and encephalitis. Mn SOD alone was significantly elevated in neurodegenerative diseases. We compared SODs with CSF levels of neuron-specific enolase (NSE) and S-100b protein (S-100b) in cerebral infarction and bacterial meningitis. Both SODs were correlated with NSE and S-100b in patients with cerebral infarction, but not in those with bacterial meningitis. This means that elevations of SODs in CSF may not only be due to leakage from damaged nervous tissues, but also to the induction of SOD in lesions. We conclude that the mean SOD levels were elevated in various neurological diseases, and their varied magnitudes may be associated with the underlying diseases.

Prognostic value of cerebrospinal fluid neuron-specific enolase and S-100b protein in Guillain-Barré syndrome.

We measured the cerebrospinal fluid (CSF) concentrations of neuron-specific enolase (NSE) and S-100b protein (S-100b) using enzyme immunoassay methods, in 24 patients with Guillain-Barré syndrome and 46 controls, and examined their prognostic values. Sixteen of 24 patients showed elevated levels (> the mean + 2SD levels of controls) of NSE, S-100b, or both, and in those with higher NSE or S-100b levels there was a rather longer duration of disease, whereas 8 patients with the normal levels showed an early recovery. Further, NSE or S-100b levels were significantly correlated with months to recovery. Thus, NSE and S-100b in CSF may be useful markers for predicting the outcome of Guillain-Barré syndrome.

[A case of "syndrome of progressive muscle spasm, alopecia, and diarrhea (Satoyoshi)" treated with steroid pulse therapy].

A 20-year-old man was admitted to our hospital because of generalized muscle cramp with pain. At the age of 12 years, he began to have painful muscle cramps in calf muscles, which gradually extended to all limb and truncal muscles and became more severe and frequent. He also had diarrhea and mild hair loss. On admission he had mild baldness, left shoulder deformity, and hypertrophic muscles. Muscle cramps were observed especially in the extremities. Routine laboratory studies revealed moderately high serum CK and low IgG levels. He had been treated with several muscle relaxants and antiepileptic drugs, but with no favorable effect. During his admission he received high-dose intravenous methylprednisone of 1000 mg/day for three days, followed by oral prednisolone tapered over 4 weeks. Soon after the initiation of the treatment, painful muscle cramps were gradually decreased and his activity of daily life apparently improved. In conclusion steroid pulse therapy is a useful treatment for patients who are not responsive to dantrolene sodium administration, and the effectiveness suggests that a certain autoimmune mechanism plays a role in pathogenetic mechanism.

[An autopsy case of chronic inflammatory demyelinating polyradiculoneuropathy with sever degeneration in the posterior column].

An autopsy case of chronic inflammatory demyelinating polyradiculoneuropathy was reported. It took a progressive course and terminated fatally in eight years. A 41-year-old man noticed motor disturbances when he tried to lift a bath pail and to write on July, 1978. Neurological examination revealed proximal dominant muscle atrophy, weakness of all extremities, and moderately diminished tendon reflex. Sensation was normal. The CSF showed albumin cytologic dissociations. Electromyogram showed neurogenic changes. Histological examination of biopsy specimen obtained from the anterior tibial muscle revealed severe neurogenic changes and showed axonal degeneration on the ventral tibial nerve. The treatment by corticosteroids was not effective, and the disease gradually progressed with repeated improvements and exacerbations. Three years after the onset, he showed vesicorectal dysfunctions. He died of respiratory failure on May, 1986. Neuropathological examination showed severe degeneration of middle root zones in the posterior columns, loss of myelinated fibers in Clarke's columns, demyelination and mild loss of axons accompanied by lymphocytic infiltration in the spinal roots, especially in the anterior roots. The histogram of cervical ventral root, ventral and dorsal roots of thoracic and lumbar regions revealed a decreased number of large myelinated fibers. A characteristic finding of this case was the dissociation of clinical features and neuropathological findings; the clinical features showed a typical motor neuropathy, but neuropathological examination showed severe degeneration on posterior columns of spinal cord like a sensory-ataxic neuropathy. Our observation suggest that the pathway which originates from posterior ganglion cells and runs into Clarke's columns passes through the middle root zones, since severe demyelination in Clarke's columns was observed.

[Cerebrospinal fluid neuron-specific enolase (NSE) and S-100b protein in Guillain-Barré syndrome--their relations to prognosis].

We measured the cerebrospinal fluid (CSF) levels of neuron-specific enolase (NSE) and S-100b protein (S-100b) using enzyme immunoassay methods in 12 patients with Guillain-Barré syndrome (GBS), and 46 control subjects, and evaluated their clinical values in relation to prognosis. The 4 patients with the remarkably elevated level of NSE or S-100b in the acute stage recovered slowly over 1 year after onset, while the 2 patients showed the normal NSE and S-100b levels and recovered within 4 months. In 6 patients, the NSE and/or S-100b were slightly or moderately increased in the acute stage. They recovered from 1.5 to 11 months after onset, and the two patients showing very early recovery have the remarkably increase of S-100b in the recovery stage. These results suggest that CSF NSE and S-100b may be useful biochemical markers for estimation of prognosis in GBS patients.

[A case of herpes zoster associated with multiple cranial nerve involvement].

A 74-year-old man who had suffered from right herpes zoster ophthalmicus developed ipsilateral multiple cranial nerve involvement two weeks later. He showed right visual disturbance, total ophthalmoplegia and peripheral facial palsy. Pleocytosis and increased protein were found in CSF. Titer of VZV antibody increased in serum and CSF. CT and MRI demonstrated no abnormal findings in the brain stem. Within a month, peripheral facial palsy improved. Severe extra-ophthalmoplegia began to improve after three months, and moderately recovered. After two and a half year, visual disturbance and mydriasis showed no improvement. In this case, we speculate that localized leptomeningitis caused multiple cranial nerve involvement.

Serum creatine kinase isoenzymes in Duchenne muscular dystrophy determined by sensitive enzyme immunoassay methods.

Serum levels of creatine kinase (CK) isoenzymes (MM, MB, and BB) were measured by sensitive enzyme immunoassay (EIA) methods in 50 patients with Duchenne muscular dystrophy (DMD) and in 39 controls. MM, MB, and BB levels in DMD patients were higher than in controls, and these three levels decreased with advancing age of DMD patients. Serum MB levels showed a good correlation with serum levels of carbonic anhydrase III (CA-III), but correlated poorly with electrocardiographic findings, suggesting that the main origin of serum MB in DMD is skeletal muscle rather than cardiac muscle.

Serum carbonic anhydrase III in myotonic dystrophy.

Serum carbonic anhydrase III (CAIII) levels were determined by means of an enzyme immunoassay method and were compared with serum creatine kinase (CK) and muscle-specific enolase (MSE) levels in 33 patients with myotonic dystrophy. Serum CAIII levels were elevated in all 33 patients, whereas serum CK and MSE levels were elevated in 12 and 10 patients, respectively. Serum CAIII levels showed a good correlation with CK levels, but a poor one with MSE levels. There was no obvious correlation between the serum CAIII level and the duration of illness or the age of the patient. These results suggest that serum CAIII is probably a more sensitive marker than CK and MSE in myotonic dystrophy and may also reflect the type 1 fiber abnormality more predominantly observed in myotonic dystrophy.

Serum carbonic anhydrase III in progressive muscular dystrophy.

Serum carbonic anhydrase III (CA-III) levels were determined by means of an enzyme immunoassay method and compared with serum creatine kinase (CK) and muscle-specific enolase (MSE) levels in 143 patients with four types of progressive muscular dystrophy (PMD), namely, Duchenne muscular dystrophy (DMD), limb-girdle dystrophy, facioscapulohumeral dystrophy and congenital dystrophy. Serum CA-III levels were raised in the majority of patients, especially in those with DMD. In DMD patients, the gradual decline in the CA-III level was observed with age. High correlations were found between CA-III, CK and MSE levels. The frequency of cases with elevated CA-III levels was the same as or greater than that of elevated CK or MSE levels in four types of PMD. These results suggest that serum CA-III may be a useful marker of muscle disease.