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Biomedical subjects

M A Tijssen

Publications and source records attributed to M A Tijssen.

16 recordsLinked to original sources
PubMed2001

Patients with the major and minor form of hyperekplexia differ with regards to disynaptic reciprocal inhibition between ankle flexor and extensor muscles.

The aim of the present study was to investigate the contribution of reciprocal inhibition to muscle tone by examining the transmission in the reciprocal inhibitory pathway in patients with a known defect in the glycine receptor. The study was performed in eight patients with hereditary hyperekplexia, six with the major form and two with the minor form of the disease. A mutation in the alpha1-subunit of the glycine receptor had been demonstrated in the patients with the major form, whereas no mutation was seen in the patients with the minor form. Disynaptic reciprocal inhibition, which is presumed to be mediated by glycine, was not seen in the patients with the major form of the disease, while it could be evoked in the patients with the minor form of the disease. Presynaptic inhibition, which is presumed to be mediated by GABA, was seen in both types of patients. It is concluded that the major form of hereditary hyperekplexia is associated with impaired transmission in glycinergic reciprocal inhibitory pathways. The findings demonstrate the importance of reciprocal inhibition for the muscle tone in man, and it is suggested that the impaired reciprocal inhibition seen in patients with a defect in the glycine receptor may contribute to the increased muscle stiffness that is observed in these patients.

Adult↗
PubMed2000

Cortical myoclonus and cerebellar pathology.

OBJECTIVE: To study the electrophysiologic and pathologic findings in three patients with cortical myoclonus. In two patients the myoclonic ataxic syndrome was associated with proven celiac disease. BACKGROUND: The pathologic findings in conditions associated with cortical myoclonus commonly involve the cerebellar system, but there has only been one report of cerebellar pathology in a patient in whom cortical myoclonus was physiologically characterized antemortem. METHODS: Cortical somatosensory evoked potentials (SEPs) were recorded and EEG activity was averaged preceding myoclonic electromyographic activity. In one patient cortico-cortical inhibition was tested using two paired ipsilateral magnetic stimuli over the motor strip. Neuropathologic examination was carried out, including linear Purkinje cell densities/millimeter calculations for different regions of the cerebellum. RESULTS: The electrophysiology showed evidence of dysfunction of the sensorimotor cortex with enlarged SEPs and a time-locked cortical potential preceding the action myoclonus. In addition, motor cortical inhibition was abnormal in one case. Pathology showed unremarkable primary sensory, motor, and premotor cerebral cortices, except for unilateral gliosis of the motor cortex in one case. The cerebellum showed patchy atrophy and ongoing degeneration. A striking feature was the greater severity of Purkinje cell loss and Bergmann gliosis in the outer aspects than in the depths of the folia. CONCLUSIONS: Pathologic abnormalities are paradoxically mainly located in the cerebellum in some patients with cortical myoclonus, despite clear electrophysiologic evidence of cortical dysfunction. This observation suggests that enhanced excitability of the sensorimotor cortex may arise as a distant effect of cerebellar pathology.

Adult↗
PubMed2000

Effects of startle and laughter in cataplectic subjects: a neurophysiological study between attacks.

OBJECTIVES: Cataplexy, when unequivocally present together with excessive daytime sleepiness, is diagnostic for narcolepsy. Unfortunately, it is difficult to induce cataplexy during consultation. In this study we tried to assess presumed subclinical expressions of cataplexy using neurophysiological tests. METHODS: In this controlled explorative study, we studied 14 patients with a clear history of cataplexy and 12 matched controls using standard H-reflex, H/M ratios, audiospinal reflex, H-reflexes modulated by emotions and startle reflexes. RESULTS: H-reflexes were attenuated during laughter in patients as well as controls. Startle reflexes were increased in patients. Audiospinal reflexes were not influenced. CONCLUSIONS: The patterns found add relevant knowledge concerning pathophysiological mechanisms and involved brain areas in cataplexy, and may reflect subclinical expressions of cataplexy. The presumed specificity of the abolishment of H-reflexes during cataplectic attacks is questioned by our findings. The exaggerated startle reflex is in line with recent findings concerning involved brain areas in narcolepsy.

Acoustic Stimulation↗
PubMed2000

Frequency analysis of EMG activity in patients with idiopathic torticollis.

The pathophysiology of idiopathic dystonic torticollis is unclear and there is no simple test that confirms the diagnosis and excludes a psychogenic or voluntary torticollis in individual patients. We recorded EMG activity in the sternocleidomastoid (SCM) and splenius capitis (SPL) muscles of eight patients with rotational torticollis and eight age-matched controls, and analysed the signals in the frequency and time domains. All control subjects but one showed a significant peak in the autospectrum of the SPL EMG at 10-12 Hz, which was absent in all patients with torticollis. Conversely, patients with torticollis had evidence of a 4-7 Hz drive to the SPL and SCM that was absent in coherence spectra from controls. The pooled cumulant density estimates revealed a peak in both groups, and within the patient group there was a second narrow subpeak with a width of 13 ms. The activity in the SCM and SPL was in phase in the patients but not in the controls. The lack of any phase difference and the suggestion of short-term synchronization between SCM and SPL are consistent with an abnormal corticoreticular and corticospinal drive in dystonic torticollis. Clinically, the pattern of SPL EMG autospectra and of SCM-SPL coherence may provide a sensitive and specific feature distinguishing dystonic from psychogenic torticollis.

Electromyography↗
PubMed1999

Hyperekplexia phenotype due to compound heterozygosity for GLRA1 gene mutations.

Hyperekplexia (MIM 149400), or startle disease, is a neurological disorder characterized by generalized stiffness during the neonatal period, excessive startle reflexes, and generalized stiffness related to the startle response. Linkage analysis mapped a major gene for this disorder to chromosome 5q33-35. Subsequently, mutations in the GLRA1 gene, encoding the alpha1 subunit of the glycine receptor, were found in hyperekplexia families with an autosomal dominant or recessive inheritance pattern. In the present study, we describe the genetic analysis of the GLRA1 gene of a family consisting of 2 children with hyperekplexia, 2 nonaffected children, and their healthy nonconsanguineous parents. Although the pedigree suggested the presence of a recessive mutation, haplotype construction showed that the 2 affected children shared the same haplotype combination in which the maternal haplotype differed from the paternal haplotype, suggesting the presence of compound heterozygosity. Mutation analysis revealed different missense mutations on the two haplotypes, changing an arginine to a histidine at amino acid positions 252 and 392, respectively. It is interesting that the hyperekplexia phenotype was only seen in individuals compound heterozygous for the two mutations, whereas family members carrying either one of the two mutations had no clinical signs.

Chromosome Mapping↗
PubMed1999

Late onset startle induced tics.

Three cases of late onset Gilles de la Tourette's syndrome are presented. The motor tics were mainly induced by an unexpected startling stimulus, but the startle reflex was not exaggerated. The tics developed after physical trauma or a period of undue emotional stress. Reflex tics may occur in Gilles de la Tourette's syndrome, but have not been described in late onset Tourette's syndrome. Such tics must be distinguished from psychogenic myoclonus and the culture bound startle syndromes.

Adult↗
PubMed1997

Startle responses in hereditary hyperekplexia.

BACKGROUND: Patients with hereditary hyperekplexia have excessive startle responses that are accompanied by transient stiffness and also continuous stiffness in infancy. A point of mutation has been identified for the major form of hereditary hyperekplexia in the gene encoding the alpha 1 subunit of the glycine receptor. OBJECTIVE: To measure startle reflexes and autonomic responses in the major form of hereditary hyperekplexia in the original Dutch pedigree. DESIGN: Startle reflexes and autonomic responses were examined by administering 3 series of 20 auditory stimuli at intervals of 10 seconds (90 and 113 dB) and 60 seconds (113 dB). SETTING: The Department of Neurology and Clinical Neurophysiology at the Leiden University Hospital, Leiden, the Netherlands. SUBJECTS: Nine patients with the major form of hyperekplexia and 20 healthy controls. Of the 9 patients, 5 took medication. The patients are part of the Dutch hyperekplexia pedigree. MAIN OUTCOME MEASURES: Startle responses were quantified with latency periods and areas of electromyographic bursts of the orbicular muscle of the eye, sternocleidomastoid and biceps muscles, and the thenar muscles. Autonomic reactions were measured with psychogalvanic responses and beat to beat changes of blood pressure and heart rate. RESULTS: The electromyographic bursts of the 4 muscles occurred in similar order in both patients and controls. The onset of the latency periods in the patient group was significantly (P < .001) prolonged in patients who took medication. Without medication, patients had shorter latency periods of the sternocleidomastoid muscle (P = .003) than controls. The electromyographic burst occurred significantly more often in patients than in controls (P < .001). The areas of the bursts were significantly larger in patients than in controls (P < .001); the degree of habituation was significantly stronger in patients than in controls (P < .001). The amplitude of the psychogalvanic response was increased in hyperekplexia, and the degree of habituation was significantly weaker in patients than in controls. Blood pressure and heart rate did not clearly react in either group. CONCLUSIONS: Motor startle responses are stronger and show more habituation in patients with hereditary hyperekplexia than in controls. The excessive responses include the psychogalvanic response. Increased responses do not necessarily indicate decreased habituation in hyperekplexia.

Acoustic Stimulation↗
PubMed1997

The effects of clonazepam and vigabatrin in hyperekplexia.

Hyperekplexia is an autosomal dominant disorder caused by a point mutation in the alpha1 subunit of the glycine receptor, characterized by excessive startle responses followed by temporary generalized stiffness. Clonazepam, effective in open case studies, potentiates, through unknown mechanisms, the neurotransmitter gamma-aminobutyric acid (GABA). Vigabatrin increases GABA by inhibition of the GABA catabolic enzyme GABA-transaminase. Effects of clonazepam (1 mg for 1 day) and vigabatrin (1000 mg per day for 5 days) were investigated in a double-blind placebo-controlled cross-over study in 4 patients with hyperekplexia. The pharmacodynamic parameters were startle reflexes, studied 3 times during the day. At each time, 2 trains of 10 auditive stimuli (113 dB) were given at intervals of 10 and 60 s. Startle movements were quantified with summed areas of EMG-bursts of the orbicularis oculi, sternocleidomastoid, biceps and thenar muscles. The degrees of stiffness and drowsiness were quantified with visual analogue scores (VAS) 10 times during the day, by both the patient and the observer. Clonazepam, but not vigabatrin, reduced startle activity significantly in both paradigms. The degree of stiffness and drowsiness was not significantly influenced by either drug.

Acoustic Stimulation↗
PubMed1997

Hyperekplexia-like syndromes without mutations in the GLRA1 gene.

Hyperekplexia (MIM: 149400), or startle disease, is an autosomal dominant neurological disorder characterized by an extreme generalized stiffness immediately after birth, normalizing during the first years of life. Other features of this disorder are excessive startle reactions to unexpected, particularly auditory, stimuli together with a short period of generalized stiffness during which voluntary movements are impossible. Linkage analysis mapped a gene for this disorder to chromosome 5q33-q35. Subsequently, mutations in the GLRA1 gene encoding the alpha 1-subunit of the glycine receptor proved to be causally related to the disease. In the present study, mutation analysis of all exon and flanking intron sequences of this gene was performed in sporadic patients and their parents. Moreover, a branch of the original Dutch hyperekplexia family with a very severely affected individual was screened for an additional mutation in the GLRA1 gene. Except for two polymorphisms, of which one results in an amino acid change, no potentially disease causing mutations were found in the alpha 1-subunit of the glycine receptor. Together with haplotype analysis these results exclude a recessive inheritance or new mutation etiology in these hyperekplexia-like syndrome and emphasize that hyperekplexia-like syndromes can be caused by other genetic factors. The involvement of other genes encoding subunits of the functional glycine receptor complex has not been excluded.

Adult↗
PubMed1996

The startle pattern in the minor form of hyperekplexia.

BACKGROUND: The major and minor forms of hereditary hyperekplexia (HE) are characterized by excessive startle responses, which are accompanied by transient stiffness only in major HE; patients with major HE also have continuous stiffness during infancy. A point mutation has been identified for major HE in the gene encoding the alpha 1 subunit of the glycine receptor but not for minor HE. OBJECTIVE: To measure startle reflexes and autonomic responses in the major and minor forms of HE in the original Dutch HE pedigree. DESIGN: Startle reflexes and autonomic responses were studied with 3 series of 20 auditory stimuli with intervals of 10 seconds (at 90 and 113 dB) and 60 seconds (at 113 dB). SETTING: A university hospital neurologic department. PATIENTS: Four patients with minor and 9 patients with major HE (patient groups) (a part of the Dutch HE family pedigree) and 20 healthy controls (control group). MAIN OUTCOME MEASURES: Startle movements were quantified with latencies and areas of electromyographic bursts of the following 4 muscles: the orbicular muscle of the eye, the sternocleidomastoid muscle, the biceps muscle of the arm, and thenar muscles. Autonomic reactions were measured with psychogalvanic responses. RESULTS. The 4 muscles contracted in similar order in the groups. The onset latencies of the orbicular muscle of the eye, the sternocleidomastoid muscle, and the biceps muscle of the arm were significantly prolonged in patients with minor HE (P < .006). The frequencies of occurrence of the electromyographic bursts were not different in the minor HE and major HE groups, but they were significantly higher in both patient groups compared with those in the control group (P < .001). The magnitude of the startle responses did not differ between the 2 patient groups (P = .4), but it was larger in both patient groups than in the control group (P < .001). Startle habituation in the minor HE group was much weaker than in the major HE group (P < .001) or in the control group (P < .001). The size of psychogalvanic responses (P = .1) and the degree of habituation (P = .24) in the minor HE group did not differ from those in the major HE group. Compared with that in the control group, the size of psychogalvanic responses in the minor HE group was larger (P < .001) and they habituated stronger (P < .001). CONCLUSIONS: The differences in the startle pattern between major HE and minor HE agree with the clinical and genetic findings: only major HE constitutes part of the HE phenotype. The cause of the minor HE is, as yet, unknown.

Adult↗
PubMed1995

[Startle disease: growing rigid with fear].

Hyperekplexia or startle disease was diagnosed in four patients, a girl of 14 months, two men of 45 and 61 years old, and a woman of 56 years old. This is an autosomal dominant inherited disorder, characterized by excessive startle reactions, notably to auditory stimuli. The four patients belong to a Dutch family in which two forms of the disorder occur. The first one is the major form, in which the startle reaction is followed by a temporary generalized stiffening of the body. These patients experience continuous generalized stiffness from birth to about the second year of life. They fall down frequently. The other is the minor form, characterized by an excessive startle reaction only.

Female↗
PubMed1995

Molecular genetic reevaluation of the Dutch hyperekplexia family.

OBJECTIVES: To confirm linkage of the locus of the major form of hyperekplexia to markers on chromosome 5q, to screen for a point mutation in the gene encoding the alpha 1 subunit of the glycine receptor, and to investigate whether the putative "minor" form of hyperkeplexia consisting of an excessive startle response without stiffness, is based on the same genetic defect as the major form. DESIGN: A survey of various symptoms of hyperekplexia was performed in the Dutch pedigree. Linkage studies were performed for these symptoms. SETTING: Subjects were visited at home, and the genetic study was performed at University Hospital Leiden, (the Netherlands). PATIENTS: A history was taken from 76 subjects in the pedigree, and neurologic examinations were performed on 61 subjects from four generations of the pedigree. MAIN OUTCOME MEASURES: The main outcome measures were lod scores for markers on chromosome 5q for the major and minor forms of hyperekplexia and periodic leg movements during sleep. Mutations in the alpha 1 subunit of the glycine receptor were detected by screening the exons with denaturing gradient gel electrophoresis. RESULTS: Exaggerated startle responses were reported in 44 patients. The major form consisted of stiffness in addition to the excessive startle reaction and occurred in 28 subjects. Sixteen of 44 subjects had startle responses without stiffness, indicating the minor form. Linkage was found between markers CSF1-R, D5S209, and D5S119 and the disease locus for the major form, but not for the minor form. The alpha 1 subunit of the glycine receptor showed a G to A transition mutation in codon 271 for the major form, but not for the minor form. CONCLUSIONS: Linkage and an abnormal glycine receptor were found only in the major form of hyperekplexia. Recognition of a major form is based on additional stiffness. This is therefore the most important diagnostic symptom. The minor form is not a different expression of the same genetic defect and may represent a normal but pronounced startle response.

Genetic Linkage↗
PubMed1995

Saccadic eye movements in hyperekplexia.

Hyperekplexia is an autosomal dominant disorder characterized by excessive startle responses followed by a temporary generalized stiffness. The startle response is generated in the medial bulbopontine reticular formation in the lower brainstem. The pulse generator of horizontal saccadic eye movements is localized in the pontine paramedian reticular formation. Measurements of horizontal visually evoked random saccades, antisaccades, and saccades toward remembered targets were performed in seven patients with familial hyperekplexia and seven health age-matched controls. The peak velocity of all three kinds of saccades was reduced (p < 0.0001) compared with that of controls. Latencies were marginally longer in the patient group (p = 0.0486). Saccadic gains did not differ between patients and controls. The ability to make antisaccades, saccades toward remembered targets, and the ability to suppress reflex saccades are similar in patients and controls. These data suggest that the origin of the excessive startle response is probably more due to a different modulation in the brainstem than to altered cortical influence.

Acoustic Stimulation↗
PubMed1993

The influence of a standard meal on Sinemet CR absorption in patients with Parkinson's disease.

We studied the influence of dietary protein intake on the plasma level profile of levodopa, carbidopa, and 3-O-methyldopa and clinical efficacy in 12 patients with idiopathic Parkinson's disease after intake of one levodopa-carbidopa 200/50 controlled release tablet (Sinemet CR; LC-CR). The tablet was given 1 h before the protein rich meal on one day (fasted) and together with the meal on an other day (non-fasted). Higher levodopa and carbidopa concentrations were reached when the LC-CR was taken 1 h before the meal, but the plasma level profile for levodopa was flatter in the non-fasted state. The area under the curve for levodopa was slightly higher in the fasted condition. For the clinical variables walking and tapping slightly better clinical results (P = 0.08) were found in the fasted condition with the higher levodopa levels. If the patient on levodopa is in a clinically satisfactory condition, then non-fasted condition could be preferred because of the smooth plasma level profile demonstrated. However, if the initial levodopa concentrations are not in the critical range to be effective for the patient, the advice should be to take the drug in a fasted condition.

Aged↗
PubMed1989

Optokinetic afternystagmus in humans: normal values of amplitude, time constant, and asymmetry.

It has been suggested that the appearance of directional asymmetry and/or a reduced time constant of optokinetic afternystagmus (OKAN) might be a clinical index of vestibular imbalance. However, we do not know the limits for OKAN parameters in normal humans. Accordingly, we studied OKAN in 30 normal subjects using a "sampling" method, in which a number of values of OKAN are obtained by turning out the lights periodically during optokinetic stimulation. We found that the initial velocity of OKAN has a large intrasubject variability. Accordingly, if precision is desired so as to obtain 95% confidence that the measured mean of the initial velocity of OKAN is within 25% of the true mean in an individual subject, at least eight measurements of the initial OKAN velocity must be taken. When 12 measurements are made, all subjects had a minimum value of 5 degrees/s initial OKAN, and there was little directional asymmetry (mean of -0.47 degree/s +/- 3.13 degrees/s). The intrasubject variability of the time constant of OKAN was similar to the variability of initial OKAN velocity. However, because it is not possible to obtain repeated measures of the time constant in a short period of time, the time constant of OKAN is less likely to be useful in clinical testing.

Adult↗