Neuroexcitatory plasma amino acids are elevated in migraine.

To investigate the role of glutamic (Glu) and aspartic acid (Asp) in migraine, we measured the plasma amino acids in migraine patients with and without aura, between and during attacks, and compared the profiles with the plasma amino acid profiles of tension headache patients and healthy controls. Between attacks, migraineurs (notably with aura) had substantially higher plasma Glu and Asp levels than did controls and tension headache patients. In addition, patients with migraine without aura showed low plasma histidine levels. During migraine attacks, Glu (and to a lesser extent Asp) levels were even further increased. The results suggest a defective cellular reuptake mechanism for Glu and Asp in migraineurs, and we hypothesize a similar defect at the neuronal/glial cell level, predisposing the brain of migraineurs to develop spreading depression.

Serotonin metabolism in migraine.

To investigate systemic serotonin (5-HT) metabolism in migraine, we determined platelet and platelet-free plasma concentrations of 5-HT, its precursors tryptophan and 5-hydroxytryptophan, and its main metabolite 5-hydroxyindoleacetic acid (5-HIAA), as well as the activities of the platelet enzymes monoamine oxidase and phenolsulfotransferase in classic and common migraineurs. Between attacks, migraineurs had lower plasma 5-HT and higher 5-HIAA levels than did healthy controls and patients with tension headache. During migraine attacks, plasma 5-HT levels were substantially higher than during attack-free periods, while 5-HIAA concentrations and platelet enzyme activities were lower. Platelet 5-HT was reduced only during common, but not classic, migraine attacks. We hypothesize that systemic 5-HT metabolism is enhanced in migraineurs during headache-free periods and transiently decreases during attacks, presumably due to a fall in enzymatic degradation. Furthermore, platelet behavior differs during migraine attacks with and without aura, and release of platelet 5-HT cannot (exclusively) be held accountable for the rise of plasma 5-HT during migraine attacks.

The hypothalamic lateral tuberal nucleus and the characteristics of neuronal loss in Huntington's disease.

Neurons in the hypothalamic lateral tuberal nucleus (NTL) were counted in 16 Huntington's disease (HD) patients and 12 controls. The control range was 47,500-71,700. In the HD cases the number ranged from 2,800 to 40,600. The log-transformed counts of the HD patients correlated closely with age-at-death (r = 0.66, P less than 0.01) and age-at-onset (r = 0.78, P less than 0.001), but not with duration of disease, nor with the severity of the neostriatal changes. Because of its vulnerability to the effects of the HD gene and its simplicity, the NTL seems fit to study the characteristics of neuronal death in HD.

Hereditary spastic dystonia: a new mitochondrial encephalopathy? Putaminal necrosis as a diagnostic sign.

A large kindred, in which either Leber's hereditary optic atrophy, or a hereditary spastic dystonia, or a combination of both manifested over many generations was restudied after the first report on it in 1964. NMR scans revealed bilateral, and, in two patients with hemidystonia, unilateral necrosis with shrinkage of the putamen, in one case associated with total disappearance of the head of the caudate nucleus. Except for age-appropriate cortical atrophy in one instance, no other changes were observed in the brain, brainstem, and cerebellum. The putaminal necrosis appears as typical "striatal slits" on the NMR scans. It is argued that this rare disease, since the princeps description in 1964 only reported in England (1986) and the U.S.A (1986), is most likely a singular type of mitochondrial encephalopathy: it is associated with Leber's optic atrophy, and the NMR changes observed have been signalled in other mitochondrial encephalomyelopathies, such as Leigh's disease and MELAS.

Non-progressive familial congenital cerebellar hypoplasia.

A syndrome is reported of congenital non-progressive, gradually slightly improving, ataxia in 3 out of 5 male sibs, issues of a first-order consanguineous mating. Additional characteristic features included: moderate microcephaly, generalised muscle weakness and hypotonia, nystagmus, and moderate mental retardation. A pyramidal syndrome of hyperreflexia and Babinski signs, without any spasticity, became manifest in the 2nd or 3rd year of life. In all three, the caudal part of the vermis was absent, the enlarged IVth ventricle opening up via Magendie's foramen into the cisterna magna. The middle and rostral vermian parts as well as the sagittal paravermian parts of the cerebellar hemispheres were hypoplastic. The differential diagnosis of this syndrome is analysed and the developmental pathogenetic mechanisms likely to produce the typifying distribution of aplasia are indicated.

Autosomal dominant adult amyotrophic lateral sclerosis. A six generation Dutch family.

A pedigree is reported in which adult autosomal dominant ALS with complete penetrance manifested in 18 individuals through 6 generations. The clinical and neuropathological details are analysed of 13 and 5 persons, respectively, from the 2nd generation onward. Onset was between the ages 19 and 46; duration of disease averaged 1.7 years. The clinical symptoms were predominantly those of initial shoulder girdle and ultimate partial bulbar muscle involvement. Neuropathological findings included, next to classical features, degeneration of various spinal tracts (as revealed most clearly with the Häggqvist procedure) and Purkinje cells loss. As accurate clinicopathological screening and the use of more than just routine staining methods indicate, presently available MND/ALS classifications accommodate actual data insufficiently.

Intrathecal immunoglobulin synthesis. Comparison of various formulae with the 'gold standard' of isoelectric focusing.

The recent introduction of a further new formula for calculating intrathecal Ig synthesis led us to compare the results of calculations obtained when using it and certain other older formulae with those of isoelectric focusing (IEF), since only the latter proves the intrathecal synthesis of oligoclonal proteins. On comparison, it was found that the results produced by the usual formulae were, without exception, inferior to those of isoelectric focusing. By using Receiver Operating Characteristic (ROC) curves, it is shown that calculations with the Reiber formula agree best with IEF. Virtually the same results are obtained with the "ln IgG index + 1" and "IgG index".

The HAF enigma: origin and clinical consequences of the appearance of high alkaline fractions on isoelectric focusing patterns of cerebrospinal fluid.

High alkaline fractions (HAF) are irregularly present on isoelectric focusing (IEF) patterns of cerebrospinal fluid (CSF). Therefore, this phenomenon was studied retrospectively in more detail. First, the appearance of HAF in time was recorded and attempts were made to discover a relationship to the biochemical parameters of CSF. No such relationship could be established, nor could any effect of age or sex of the patients or any correlation with ambient temperature or clinical diagnosis be shown. Finally, we have shown conclusively that the cause of this random appearance of HAF can be found in the collodion bags used to concentrate the CSF. This irregular feature of the collodion bags also produces a rise in the frequency of appearance of oligoclonal bands on IEF, probably by blocking the passage of proteins. We conclude that the CSF contains protein material, and that the passage of this through the collodion filters during CSF concentration depends on the regularity of composition of the filters used, occasioning the presence (or absence) of a HAF. Of even greater consequence is the observation that when HAFs do not pass a certain collodion filter, other protein-like material can also be retained, leading to the appearance of oligoclonal bands in IEF, and causing more frequent occurrence of IEF patterns containing oligoclonal bands in CSF. Also, a slight change in the spectrum of oligoclonal bands of CSF has been found when HAFs occur. This indicates that the collodion bags do not retain all protein material in the same way.

Hereditary spastic dystonia with Leber's hereditary optic neuropathy: neuropathological findings.

Neuropathological findings in a 59-year-old male case of hereditary spastic dystonia with Leber's hereditary optic atrophy included: marked depletion of myelinated nerve fibres in the posterior funiculi, corticopontine tracts and striatum; practically complete neuronal depletion in the putamen and lateral part of the caudate, and mild cell loss in the substantia nigra. The putamina had changed into a spongy fibrillary scar, the pallidal fibres and laminae were practically all degenerated. Moreover, there was generalised mild fibre degeneration of the white matter. The optic nerve showed marked, predominantly central, loss of nerve fibres with demyelination.

An unusual CT-scan appearance in multiple sclerosis.

Case report on a woman aged 28 years with acute multiple sclerosis. At presentation the symptoms were few and mild: frontal headache with occasional vomiting, slight speech-difficulties, increased sleepiness and slight disorientation with confusion. CT scanning revealed multiple, ring-forming hypodense lesions throughout both cerebral hemispheres suggestive of metastases.

Intrathecal Ig synthesis. Its detection by isoelectric focusing and IgG index.

In a retrospective study on 999 patients, the likelihood ratios of the IgG index, Tourtellotte formula and IgG concentration in CSF and in serum, the albumin concentration in CSF and in serum, and the total protein in CSF, were compared in predicting intrathecal Ig synthesis. This synthesis was detected with isoelectric focusing (IEF). No patient was included more than once in the data collection. All patients with high IgG and other abnormalities in serum, as well as all xanthochromic and blood-tinged CSF specimens, were excluded from the study. Construction of ROC curves established that the IgG index, Tourtellotte formula and CSF IgG yield the same information: these parameters indicate the presence of intrathecal IgG synthesis. The likelihood ratio for the IgG index at a cut-off point of 0.80 for a positive test is 20; at a cut-off point of 0.5 for a negative test it is 5. For the Tourtellotte formula, it was found that the likelihood ratio reached a maximal value of 7 at a cut-off value of synthesis of 10 mg/day for a positive test. For a negative result, the formula had a likelihood ratio of 6 at a cut-off value of -5. For CSF IgG, it was found that the likelihood ratio was 4 for a positive test with a cut-off value of 0.1 g/l. For a negative outcome, the determination of CSF IgG is only meaningful at a very low cut-off value (0.03 g/l). The other parameters studied (serum IgG concentration, albumin concentration in CSF and in serum, and total protein in CSF) showed a likelihood ratio equal to 1. It is concluded that only the IgG index, the Tourtellotte formula and the CSF IgG concentration have predictive value for intrathecal Ig synthesis as recorded with IEF.

Dipyridamole attenuates the development of iminodipropionitrile-induced dyskinetic abnormalities in rats.

The present investigation was undertaken to study the effect of dipyridamole on experimental dyskinesia in rats. The movement disorders were produced by intraperitoneal administration of iminodipropionitrile (IDPN) in the dose of 100 mg/kg per day for 12 days. Dipyridamole was administered orally, daily 30 min before IDPN in the doses of 0.5 g/kg, 1 g/kg, and 1.5 g/kg bodyweight in three different groups of rats. Twenty-four hours after the last dose of IDPN, animals were observed for neurobehavioral changes including vertical and horizontal head weaving, circling, backwalking, grip strength, and righting reflex. Immediately after behavioral studies brain specimens were collected for analysis of vitamin E, conjugated dienes, and lipid hydroperoxides as indices of oxygen-derived free radical (OFR) production. Our results showed that concurrent use of dipyridamole significantly protected rats against IDPN-induced neurobehavioral changes in a dose-dependent manner. Treatment of rats with dipyridamole inhibited IDPN-induced decrease of vitamin E and increase in conjugated dienes and lipid hydroperoxides in brain. These findings suggest the involvement of OFR in dipyridamole induced protection against the development of IDPN dyskinesia. Further studies are warranted to determine the role of dipyridamole as a prophylactic agent against the drug induced dyskinetic abnormalities.

Biparietal osteodystrophy.

Following an exhaustive literature review of 126 cases, a personal series of 8 instances is presented. The following inferences are drawn: 1) the condition is not an anatomical variant, but a pathological lesion. 2) the lesion occurs in all races, and at all latitudes; its prevalence can be estimated to range between 0.4 and 0.5%. 3) the lesion occurs predominantly in females (sex ratio male: female = 1 : 2.5) and after the age of 60. 4) histological evidence indicated erosion of the external table, compensated by remodeling of the diploe, with resultant loss of the diploe. 5) Neither senility nor senescence, nor chronic trauma, nor muscular traction, nor inflammation, can explain the lesion, its symmetry, its site or its age/sex predilection.

Senile plaques in Huntington's disease: a preliminary report.

The brains of 10 patients with Huntington's disease (HD) were studied for the presence of senile plaques (SP), neurofibrillary tangles, and granulovacuolar degeneration in the frontobasal, the parietal and occipital cortices and the anterior and posterior hippocampus. Five had died at a mean age of 42 years and 5 at one of 74 years. Senile plaques were found in 3 of 5 elderly HD patients and no were found in the young group. This finding supports the hypothesis that dementia in HD is not related to the presence of senile changes of the Alzheimer type.

A forme fruste of the pterygium syndrome?

A case of a girl with popliteal webbing associated with limited extension of the knee, flexion contractures of the third, fourth, and fifth digits, hypothrophia of leg musculature, and absent tendon reflexes in the legs is reported. Between 19 months and 6 years of age, the digital contractures, popliteal webbing, and limitation of knee extension progressively improved. This is the first reported instance of this combination of signs and the first report of regression of some of these physical findings.

A century of Dutch neurology.

The Netherlands Society of Neurology evolved from the Society of Psychiatry founded in 1871. The name was changed into Netherlands Society of Psychiatry and Neurology (NSPN) in 1897. In the same year, the word neurology was also added to the name of the journal. The Society steadily blossomed, but in 1909 the first signs of dissatisfaction occurred: the Amsterdam Neurologists Society was founded. A few split-offs would follow. The number of members of the NSPN increased from 205 in 1920 to 585 in 1960. In the early 1960s, the Society was reorganised and would consist of two sections, one for psychiatry and one for neurology. However, this would not last, as a full separation was established in 1974. For several reasons, the name of the journal was changed four times until it assumed its present name in 1974. The 100th volume of CNN was not published, as expected. in 1996, but in 1998, because of two skipped publication years, one during WWII and another in the 1970s. During the last decades of the nineteenth century, teaching of neurology was mostly given within the frame of psychiatry, following the German tradition of 'brainpsychiatry' (organic or biologic psychiatry). The first official chair of psychiatry was founded at Utrecht, 1893 (Winkler). In Amsterdam, private teachers such as Delprat taught 'electro-therapy and nervous diseases' since the 1880s. The first extraordinary chair of neurology and electrotherapy was founded for his successor, Wertheim Salomonson in 1899. The first university clinic for psychiatry and neurology started at the Amsterdam Municipal University, when Winkler became professor of psychiatry and neurology in Amsterdam in 1896. Around the turn of the century, chairs of psychiatry and neurology were also founded in Groningen and Leiden. Separate chairs for neurology and psychiatry appeared in Amsterdam in 1923 and in Utrecht in 1936. Following an initiative of Brouwer, the first neurological university clinic opened its doors in Amsterdam in 1929. In the 20th century, a number specialised peripheral neurological clinics and epilepsy institutes were founded. In 1909, the the Central Institute for Brain Research was established in Amsterdam.

The use of and familiarity with neurological eponyms at the close of the 20th century by Dutch neurologists. An inventory.

In order to get an impression on the opinion of the use of neurological eponyms we sent questionnaires on 205 eponyms to 850 members of the Netherlands Association for Neurology. The responses by 256 (30%) were analyzed. A positive correlation was found between age and the knowledge of eponyms. The best known eponyms belong to category II (tests and manoeuvres). Surprisingly, many of the responding colleagues did not prefer descriptive terms to eponyms: 57% of the eponyms were preferred by more than 50% of the respondents.

Further observation on the possible relationship between migraine and serum ammonia levels.

Although patients diagnosed as having migraine, have been studied extensively, there is no definite proof of a primary biochemical abnormality which is of significance in the pathogenesis of migraine. Several authors have suggested that increased serum ammonia levels may play a decisive role in the pathogenesis of migraine. This possibility was first put forth by Russell, who studied a single family with ornithine carbamyl transferase deficiency and 8 juveniles with migraine, RUSSELL'S finding was supported by a preliminary study carried out by one of the authors in which hyperammo-naemia was found in 22 adults during migraine attacks. In order to etknd these earlier findings, serum ammonia levels were determined in 35 adults with either classic or complicated migraine and in 20 healthy adults. No significant difference was found between the patients (44 microgram/100 ml +/- 13.9) and the controls (74 microgram/100 ml +/- 9.5). Ammonia level was determined in 10 patients within two hours of the onset of an acute migraine and was unchanged (65 microgram/100 ml). This study suggests that alterations in serum ammonia level are not important in the pathogenesis of migraine in adults.

Migraine, Tolosa-Hunt syndrome and pleocytosis. Correlation or coincidence?

A critical analysis is presented of the problem whether the migraine attack causes CSF-pleocytosis or vice versa, on the basis of a series of 3 cases, including one of Tolosa-Hunt syndrome due to sarcoidosis, the other two ultimately showing chronic leptomeningitis. The evidence leads to the conclusion that migraine does not cause pleocytosis and pleocytosis does not cause migraine: both are correlated by an underlying common denominator.

Altered postural reflexes in Parkinson's disease: a reverse hypothesis.

In subjects standing on a movable platform, sudden dorsiflexion of the ankle joint elicits a set of reflexes in leg muscles. These responses include a short latency (SL) and medium latency (ML) stretch reflex in the gastrocnemius muscle and a distal to proximal innervation sequence of long latency (LL) reflexes in the shortened tibialis anterior and vastus lateralis muscles. Because of their role in maintaining upright stance these responses have been termed postural reflexes. In patients with Parkinson's disease (PD), the following abnormalities have been described: 1) enhanced ML-amplitudes; 2) a reversed LL innervation sequence; and 3) delayed onset latencies. These abnormalities are thought to be due to defective motor programming and disturbed control of spinal and supraspinal reflex centers by basal ganglia circuits. The altered reflexes have been held responsible for some of the clinical features of PD, including balance impairment and rigidity. In this paper, we argue the reverse hypothesis that postural reflexes are essentially normal in PD, and that the observed alterations are at least in part consequence rather than cause of balance impairment, the stooped parkinsonian posture and rigidity of PD patients.