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The European radiotherapy society has for many years had a great interest in quality assurance. The EORTC radiotherapy group has put enormous effort into its quality assurance programmes. However, besides programmes for dosimetry and guide-lines for infrastructure, the organisation of a department should also be subject to a quality assurance system. In 1992, in the radiotherapy department in Leiden, a project was started to develop a quality assurance system based on the so-called ISO 9001 quality standards. This paper describes how these standards can be applied to create a quality assurance system in a hospital department.

Radioiodinated spiperone is of interest for dopamine (DA) receptor studies in the living human brain by single photon emission computed tomography (SPECT). Stimulated by data obtained with [11C]-N-methyl-spiperone we synthesized 4-[123I]iodospiperone and investigated the in vitro binding characteristics of this ligand to the striatal membrane of the rat and the in vivo distribution over various rat brain regions. The in vitro binding experiments showed that this radioligand displays about 10 times less affinity for the DA receptor than spiperone and specific binding, as shown with [3H]spiperone, was not observed. Displacement by butaclamol was not observed. The in vivo studies demonstrated that both 4-[123I]iodospiperone and [3H]spiperone concentrate in striatal tissue, respectively, 1.9 and 3.5 times as high as in cerebellar tissue. Haloperidol pretreatment largely prevented this accumulation. In view of the obtained target-to-non-target ratios we believe, however, that this accumulation in brain areas rich in DA-receptors does not offer prospects for clinical receptor imaging with SPECT.

In view of reported associations between increased bleeding tendency and systemically decreased alpha 2-antiplasmin in patients with systemic amyloid deposition we studied alpha 2-antiplasmin, fibrinogen, C-reactive protein and blood levels of locally produced endothelial hemostasis factors in the acute and quiescent phase in 16 patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). None of the factors measured in the quiescent phase of the disease was abnormal. In the acute phase, shortly after a stroke, only factor VIII:Ag was evidently elevated. We concluded that systemic abnormalities in the part of the fibrinolysis system studied are not likely to be responsible for multifocal and recurrent cerebral hemorrhages in HCHWA-D. The role of an elevated factor VIII:Ag level in the acute phase is unclear.

Evaluations were made of the diurnal variations of tremor power at rest, after fatigue and after mass loading, and plasma norepinephrine in patients with familial essential tremor and normal subjects. Diurnal tremor power rhythms for both essential and physiological tremor pursued identical temporal profiles. Plasma norepinephrine levels followed a congruent diurnal pattern with later peak values than the peak values of tremor power. Sympathetic nervous system activity is unlikely to be the cause of diurnal tremor power variation. The consistent diurnal rhythm of tremor power may affect dosage schemes of tremorolytic drugs.

Prosodic features in the speech production of 21 patients with idiopathic Parkinson's disease were tested. The appreciation of vocal and facial expression was also examined in the same patients. Significant intergroup differences were found in the prosody production tasks but, in contrast to previous results, not in the receptive tasks on the recognition and appreciation of prosody and of facial expression. The discrepancy between the production and recognition of prosodic features does not support the suggestion that dysprosody in Parkinson's disease is necessarily a disorder of processing emotional information that could be misinterpreted as a dysarthria.

In human and subhuman primates, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces irreversible clinical, biochemical and neuropathological alterations highly reminiscent of those observed in Parkinson's disease. The MPTP model has provided the best available tool to date for the assessment of efficacy and side-effects of symptomatic treatments of Parkinson's disease. In addition, the mechanism of action of MPTP has offered a basis for the development of novel therapeutic strategies aimed at the prevention of Parkinson's disease.

Phenytoin-parahydroxylation capacity was determined in 24 patients with Parkinson's disease (PD) and 17 controls. Different function of the phenytoin-metabolizing cytochrome P450 subsystem was found in 6 patients, but in none of the controls. These results add to previous studies suggesting a relation between the pathogenesis of PD and the function of cytochrome P450 subsystems.

Lymphocyte capping with concanavalin A was studied in 11 patients with hereditary cerebral haemorrhage with amyloidosis (Dutch type) and 10 controls. No difference in capping was found between patients and controls. Abnormal lymphocyte concanavalin A capping has been reported in patients with the Icelandic type of cerebral amyloidosis and in patients with Alzheimer's disease, a disease in which cerebral amyloid angiopathy can also be found. The results suggest a difference in pathogenesis between the Dutch type of cerebral amyloidosis and the other amyloid diseases.

We performed single photon emission computed tomography (SPECT) and cerebral CT-scans in nine patients with hereditary cerebral amyloid angiopathy. CT-scans showed 23 focal hypodense lesions, 13 of which were visible on SPECT as a CBF-defect. One patient showed a CBF-defect on SPECT without CT-scan lesion and had a cerebral hemorrhage three months later in that particular region. In two additional patients, who were 50% at risk for this autosomal dominant disease, CBF-defects on SPECT, but no cortical lesions on CT-scan were found. CT-scans may be more sensitive than SPECT to detect chronic lesions caused by cerebral hemorrhages, but another possibility is that hemorrhages do not always lead to persistent CBF-defects. SPECT can show the effect of amyloid deposits on CBF before the angiopathy causes clinical symptoms.

A patient is described, with a history of pain in the neck, followed by a slowly progressive loss of muscle strength in both arms, followed by tetraplegia. Medical history included laryngectomy with partial hypopharyngectomy preceded by radiotherapy, because of carcinoma. X-ray of the cervical spine was suggestive for metastases. The patient died as a consequence of massive pulmonary embolism and at autopsy the cause of the neurological deficit turned out to be vertebral osteomyelitis and epidural abscess due to mucormycosis.

The effect of Tiapride on dyskinesia was evaluated in 12 patients with tardive dyskinesia in a double-blind controlled cross-over trial. The effect was measured by a Doppler-radar device and by counting the number of involuntary movements from video-recordings. Besides these methods, subjective assessments were made on analogue scales by family, nurses and attendant doctors. The subjective evaluation appeared to be useless because of many inconsistent answers. The quantitative methods revealed a significant diminution of the involuntary movements in the Tiapride therapy period (P less than 0.01). It appears that tiapride is an effective drug in the treatment of tardive dyskinesia. No clinically important side-effects have been observed. The drug appeared not to induce parkinsonism.

A patient is described, with a history of sudden headache and vomiting, without major neurological deficit. There was no history of trauma. The cause turned out to be an acute spontaneous bilateral subdural hematoma. Comparable cases in literature and the etiological possibilities are discussed.

A case history is presented of a patient who developed a severe phenytoin intoxication on a "therapeutic" dose of 300 mg/day. This phenomenon could be ascribed to a poor oxidative metabolizing capacity of this patient for phenytoin, as demonstrated by a low para-hydroxyphenyl-phenylhydantoin to phenytoin ratio in the urine. To characterize the specificity of this metabolic defect, debrisoquine and antipyrine oxidation were also studied. Contrary to expectations, this patient was shown to be an extensive debrisoquine metabolizer; the antipyrine clearance was even higher than normal. These findings suggest that phenytoin para-hydroxylation is regulated by an oxidative enzyme complex different from those which oxidize debrisoquine and antipyrine.

Central nervous system (CNS) involvement in mycosis fungoides (MF) usually occurs in the presence of active skin lesions and infiltration of many visceral organs. A case of MF is presented, associated with a neurological syndrome, characterized by ataxia and motor-neuron disease. Autopsy revealed widespread infiltration of the CNS by MF, in the presence of only one minimal skin lesion and with no involvement of visceral organs. The importance of being aware of this discrepancy is stressed in the light of the possibility of radiotherapy in CNS involvement.

Twenty-two patients with Huntington's chorea were investigated in a double-blind controlled cross-over trial. The effect was measured by counting the number of involuntary movements from video-recordings and by a Doppler-radar device. Besides these methods, subjective assessments were made on analogue scales by patients, family, nurses and attendant doctors. The quantitative methods revealed no significant diminution of the involuntary movements in the Tiapride therapy period. The subjective evaluation turned out to be useless because of many inconsistent answers.

Blink reflex, corneal reflex, jaw reflex, exteroceptive suppression in masseter muscles and brainstem auditory evoked potentials were measured in 20 patients with Huntington's chorea and 12 controls. A significantly increased latency of the second component of the homolateral and heterolateral blink reflex was found in the patient group as compared with the controls. The other investigations revealed no significant differences between patients and controls except for some facilitation of the jaw reflex in the patient group. Increase of second component latency of the blink reflex in the presence of normal corneal reflexes is suggestive of functional impulse conduction disturbance in the lower brainstem. It is discussed whether in Huntington's chorea this is to be attributed to alterations of cortical or striatal influence or to local brainstem abnormalities.

Autonomic nervous system function was studied by means of a series of standardized tests in 11 patients with Huntington's disease (HD) and in 11 age- and sex-matched controls. Two statistically significant differences were found. The blood pressure response to sustained handgrip was diminished and the pupillary light reflex latency was increased in the HD group. The former probably reflects diminished input from higher centers on an otherwise intact sympathetic nervous system. The latter may indicate involvement of the pretectal or Edinger-Westphal nuclei in HD. No further signs of autonomic nervous system dysfunction were found.

In a 32-year-old female areflexia occurred after thoraco-lumbar myelography with metrizamide (Amipaque), instead of the hyperreflexia usually found as a side effect of subarachnoid water-soluble contrast media. A direct neurotoxic effect on the cauda equina seems to have been the cause.

Computed tomography fails to ascertain, or exclude, the presence of intracranial haemorrhage in a considerable number of cases, especially in subarachnoid haemorrhage and haemorrhagic infarcts. A number of other methods, including cerebrospinal fluid spectrophotometry and cytology have, therefore, been tested to define their diagnostic efficacy in 25 cases of confirmed intracranial haemorrhage and in 25 instances of blood-stained cerebrospinal fluid due to traumatic puncture. The combination of spectrophotometry and cytology proved to have a high diagnostic reliability. On the basis of these results a routine scheme of investigation is proposed.

The results are reported of cardiological examinations, including echocardiography, in nine members of a family suffering from hypokalaemic periodic paralysis, associated with permanent muscular weakness. The studies were performed in periods between attacks of paralysis. The slowly progressive permanent muscular weakness which is found in most of the patients with hypokalaemic periodic paralysis resembles a limb-girdle type dystrophy. Involvement of cardiac muscle is not uncommon in patients with limb-girdle dystrophy. Using a combination of echocardiography and ECG examination, nowadays the most sensitive screening method for the detection of cardiomyopathy, no evidence was obtained for cardiac involvement in hypokalaemic periodic paralysis patients with permanent muscular weakness.

Fibrocartilaginous embolism of the spinal cord has been reported in only 17 cases. We describe three new cases, all seen within a year, of infarction of the spinal cord by fibrocartilaginous emboli in the ramifications of the anterior spinal artery. These emboli probably originate from degenerated intervertebral disks, but full understanding of the pathogenesis is still lacking. The disease has been found more frequently in dogs. Because the pathologist is not likely to attempt to demonstrate the condition unless the clinician has proposed this diagnosis, the true frequency will be known only when the clinical picture is widely recognized.

With a tv-based computer system, using reflective markers attached to 4 subjects' right index fingers, peak velocities were measured of fast hand movements in both directions between a midline target and left and right sided targets. Peak velocity increased with distance. Movements between the midline and the right sided target (ipsilateral) were faster than those between the midline and left sided target (contralateral). Adduction movements were faster than abduction movements. Retesting two subjects showed a high degree of variability in the peak velocities attained, but the same pattern of faster ipsilateral and adducting movements was found.

A large family with hypokalemic periodic paralysis was reexamined after 50 years. Two new cases were found in the third generation and 12 in the fourth generation. This family now includes 28 affected patients in four generations. The reexamination ascertained the presence of permanent muscle weakness (PMW) in all investigated affected sibs. This fact, and the fact that indications of the presence of PMW without paralytic attacks were found in only one subject, is strong evidence that both are manifestations of the same more or less fully penetrant dominant gene. A linkage study in this family could not localize the gene on the human genome, but close linkage with 25 genetic marker systems could be excluded.

A study of RBC membrane functions was performed in four patients suffering from familial hypokalemic periodic paralysis who had permanent muscular weakness. Electrophoretograms of membrane proteins, cell deformability, calcium-promoted potassium efflux, calcium-ATPase activity, and endogeneous phosphorylation of membrane proteins were all within the normal range. These results are compared with similar studies performed in myotonic and Duchenne-type dystrophies, in which abnormalities in the RBC membrane have been described. The results do not support the theory of RBC involvement in hypokalemic periodic paralysis. However, this does not imply that the muscle cell membrane is not involved in the underlying pathological processes in this disorder.

An oral glucose tolerance test (OGTT) was performed in 1985 in 10 patients with Huntington's disease (HD), while 10 healthy age-matched volunteers served as controls. Two-and-a-half years later, in 1988, 8 of the original 10 patients were reinvestigated. Apart from glucose, insulin and growth hormone (sampled at 30 min intervals) the following parameters of endocrine function were assessed: C-peptide (at times 0 and 60 min), glycosylated haemoglobin (HbAlc), somatomedin-C, and basal prolactin. In 1985 one female patient was considered to have impaired glucose tolerance, and this same patient, as well as another male patient, had a paradoxical rise in GH secretion. None of the other measurements of endocrine function differed significantly from control. In 1988 the HD patients had clinically deteriorated significantly, as measured by the Shoulson and Fahn Scale. Six of them completed a repeat OGTT. Of these 6, the same female as in 1985 showed impaired glucose tolerance. Now none of the participants had a paradoxical GH rise. The HD patients did not show any deterioration of the parameters of glucose metabolism, nor of GH secretion. The basal prolactin level, however, decreased significantly in these 2.5 years, from 9.3 +/- 3.2 micrograms/l to 6.1 +/- 3.0 micrograms/l (P less than 0.01).

In view of recent reports on lower brainstem dysfunction in Huntington's chorea, we studied respiration during sleep in 12 patients with Huntington's chorea (HC) and in controls. There were no statistically significant differences between patients and controls with respect to apnea periods, respiratory frequency and time elapsed between minimal and maximal value of the respiratory curve. No statistically significant differences in respiratory variability were observed between patients and controls. In the present study, no indication was found for dysfunction of lower brainstem structures involved in respiration in HC.

With a newly developed infrared reflection technique, voluntary saccadic eye movements (VOLS), visually evoked saccades (VES) and unsuppressed visually evoked reflex saccades (USVERS) were measured in 11 patients with Huntington's chorea. Abnormalities, including latency increase, peak velocity decrease and undershoot dysmetria with multiple step saccades were found in all types of saccadic eye movements. Peak velocity decrease and undershoot dysmetria can be explained by dysfunction of the brainstem reticular formation in Huntington's chorea. USVERS and square wave jerks occurred abnormally frequently and showed direction-dependent differences. Both were more frequent in horizontal than in vertical direction. Frequency of USVERS and square-wave jerks tended to be correlated. These findings point to disinhibited superior colliculi as a possible common supranuclear origin of USVERS and square-wave jerks in Huntington's chorea.

The case history, skeletal muscle and heart muscle biopsy findings from an affected member of a family suffering from hypokalaemic periodic paralysis associated with permanent muscular weakness are reported. The patient, a female aged 35 years, while treated with 750 mg and later 1000 mg of acetazolamide daily, developed typical exercise angina pectoris. The ECG during exercise showed ST-segment depression. A coronary angiography was performed because coronary artery disease was suspected. To exclude cardiac muscle disease a biopsy of the left ventricular wall was taken. The angiography was normal. Ultrastructural analysis of the biopsy specimen showed an unusual amount of intermyofibrillary glycogen resembling, although far less abundant, the increase of glycogen found in the skeletal muscle biopsy specimen obtained from the same patient. The possible implications of these findings are discussed with reference to the normal echocardiographic findings in the family.

The pharmacokinetics of tiapride were determined at steady-state in 5 patients with tardive dyskinesia and 2 patients with Huntington's disease given tiapride 100 mg t.i.d. for 7 days. The maximum serum concentration of tiapride of 1.47 +/- 0.35 micrograms/ml was reached after 1.4 +/- 0.67 h. The half-life time of elimination was 229 +/- 41 min. About 50% of the dose of tiapride was excreted unchanged by the kidney. Neither protein binding nor glucuronide, sulphate or acetyl conjugation was observed. Renal clearance in the patients appeared to be lower but the other pharmacokinetic parameters did not differ from previous findings in healthy young volunteers.

Five patients with a cutaneous T-cell lymphoma (four with mycosis fungoides and one with a primary cutaneous T-immunoblastic lymphoma) who developed neurological sequelae are reported. In four of them, central nervous system involvement could be demonstrated at autopsy. The importance of early cerebrospinal fluid examination in these patients is stressed.

Somatosensory evoked potentials were measured in 21 patients with Huntington's chorea and 12 controls. Central brain conduction time was normal. Early cortical component amplitudes were reduced in the patient group, latencies were normal. These abnormalities probably can be attributed to cortical dysfunction in Huntington's chorea. No indication of brain-stem dysfunction was found.

Saccadic eye movements, fixation and smooth pursuit were studied in 28 children with Gilles de la Tourette syndrome and found to be normal. A link has been postulated between Gilles de la Tourette syndrome and other movement disorders. The results obtained in the present series do not support this hypothesis.

Ten patients with tardive dyskinesia were treated with tiapride at an increasing dosage to establish the dose-concentration relationship and the dose-effect relationship. The effect was scored with the Abnormal Involuntary Movement Scale (AIMS) and the Doppler-radar method. The intra individual dosage-serum concentration correlation coefficients varied from 0.86 to 0.99 and the slopes of the individual regression lines varied from 0.16 to 0.58. All patients showed a diminution of their involuntary movements during the treatment period. A negative correlation coefficient was found between the dosage of tiapride and the AIMS; range -0.22 till -0.93, mean: -0.65 +/- 0.23 (SD). The Doppler-radar method results were inconclusive. No side-effects were observed.