Electroencephalography in autosomal dominant adult neuronal ceroid lipofuscinosis.

OBJECTIVE: To describe the findings in 59 EEGs from six patients from three generations in a family with autosomal dominant adult neuronal ceroid lipofuscinosis (Parry disease), autopsy proven, with a follow up of 9-21 years. METHODS: Descriptive, visual EEG analysis. RESULTS: In these patients with epilepsy, myoclonus, dementia and Parkinsonism, EEGs were all severely abnormal, with generalized or bilateral independent periodic epileptiform discharges as the most common pattern. In a few EEGs periodic discharges were seen. No alpha rhythm was present. No paroxysmal response to photic stimulation was seen. Intraindividual EEG changes in the course of the disease were modest, despite severe clinical disease progression. No cortical component linked to myoclonus could be found with a backaveraging technique. CONCLUSIONS: EEG in autosomal dominant neuronal ceroid lipofuscinosis is dominated by generalised periodic epileptiform discharges (GPEDs, or GPD+). SIGNIFICANCE: GPD/GPEDs in adults with myoclonus, Parkinsonism, dementia or epilepsy should raise the possibility of adult neuronal ceroid lipofuscinosis, especially with familial occurrence.

Recovery of posterior communicating artery aneurysm-induced oculomotor palsy after coiling.

BACKGROUND AND PURPOSE: Recovery of oculomotor (cranial nerve [CN] III) palsy after surgery of posterior communicating artery (PcomA) aneurysms has been well documented, but recovery after coiling is poorly understood. In this study, we report the recovery after coiling of PcomA aneurysm-induced CN III palsy in 21 patients at follow-up of 1 to 7 years. MATERIALS AND METHODS: Of 135 patients with a PcomA aneurysm treated with coils between January 1997 and December 2003, there were 21 patients with initial CN III dysfunction who were selected and reevaluated. There were 2 men and 19 women with a mean age of 54.9 years. In 17 patients, CN III palsy was associated with subarachnoid hemorrhage (SAH). Timing of treatment after onset of symptoms was 1 to 3 days in 5 patients, 4 to 14 days in 13, and more than 14 days in 3. Mean size of the aneurysm was 9 mm. Initial CN III palsy was complete in 15 patients and partial in 6. Mean follow-up after coiling was 3.7 years (range, 1-7 years). RESULTS: Of 15 patients with initial complete CN III palsy, recovery was complete in 3 and partial in 10. In 2 patients, complete CN III palsy was unchanged. Of 6 patients with initial partial CN III palsy, recovery was complete in 5 and partial in 1. Initial partial CN III palsy was the only predictor of complete recovery at follow-up. CONCLUSION: PcomA aneurysm-induced CN III palsy improves or cures after coiling in most patients. Complete recovery is more likely with initial partial dysfunction of the nerve.

Procedural complications of coiling of ruptured intracranial aneurysms: incidence and risk factors in a consecutive series of 681 patients.

BACKGROUND AND PURPOSE: To report the incidence of procedural complications of coiling of ruptured intracranial aneurysms leading to permanent disability or death in a consecutive series of 681 patients and to identify risk factors for these events. PATIENTS AND METHODS: Between January 1995 and July 2005, 681 consecutive patients with ruptured intracranial aneurysms were treated with detachable coils. Procedural complications (aneurysm rupture or thromboembolic) of coiling leading to death or neurologic disability at the time of hospital discharge were recorded. For patients with procedural complications, odds ratios (OR) with corresponding 95% confidence intervals (CI) were calculated for the following patient and aneurysm characteristics: patient age and sex, use of a supporting balloon, aneurysm location, timing of treatment, clinical condition at the time of treatment, and aneurysm size. RESULTS: Procedural complications occurred in 40 of 681 patients (5.87%; 95% CI, 4.2% to 7.9%), leading to death in 18 patients (procedural mortality, 2.6%; 95% CI, 1.6% to 4.2%) and to disability in 22 patients (procedural morbidity, 3.2%; 95% CI, 2.0% to 4.9%). There were 8 procedural ruptures and 32 thromboembolic complications. The use of a temporary supporting balloon was the only significant risk factor (OR, 5.1; 95% CI, 2.3 to 15.3%) for the occurrence of procedural complications. CONCLUSION: Procedural complication rate of coiling of ruptured aneurysms leading to disability or death is 5.9%. In this series, the use of a temporary supporting balloon in the treatment of wide-necked aneurysms was the only risk factor for the occurrence of complications.

Coiling of truly incidental intracranial aneurysms.

BACKGROUND AND PURPOSE: The purpose of this study is to report the morbidity, mortality, and angiographic results of coiling of asymptomatic incidental aneurysms and compare the characteristics of these aneurysms with other asymptomatic incidental aneurysms that were not treated. PATIENTS AND METHODS: During a 10-year period, 97 patients without previous subarachnoid hemorrhage, presented with incidentally found intracranial aneurysms. In 48 patients, 58 aneurysms were coiled. The mean size of the 58 coiled incidental aneurysms was 10.9 mm (median, 9 mm; range, 3-40 mm). Twenty-six of 58 coiled aneurysms (44.8%) were > or = 10 mm. RESULTS: Permanent morbidity of coiling was 2.1% (1 of 48), mortality was 0%. Compared with untreated patients with incidental aneurysms, coiled patients were younger and more often had multiple aneurysms. Aneurysms of coiled patients more often had a small neck, were more often located on the carotid artery, and were less often located on the middle cerebral artery. Of 46 aneurysms with angiographic follow up, 45 were completely or near completely occluded. To obtain these results, 3 aneurysms were coiled more than once. Coiled incidental aneurysms did not rupture during a median follow-up period of 28.5 months. Mean hospital stay per patient was 2.5 days. CONCLUSION: Coiling of incidental intracranial aneurysms has a low complication rate in selected aneurysms and patients. Coiling should be the first treatment option in incidental aneurysms suitable for this technique.

[Progressive ataxia and cognitive deficits caused by premutation in the fragile-X-mental retardation gene]. / Progressieve ataxie en cognitieve achteruitgang door een premutatie in het fragiele-X-mentale-retardatiegen.

A 75-year-old man had progressive difficulty with walking, intention tremor, ataxia, and mild cognitive deficits. MRI scan ofthe brain showed symmetrical hyperintensities in the middle cerebellar peduncles. DNA analysis ofthe fragile-X gene revealed an expansion of 150-200 repetitions in the FMR1-gene, compatible with a premutation in the fragile-X gene. Two years later, after progression of the symptoms, the patient was admitted to a nursing home. The clinical picture of intention tremor, parkinsonism and ataxia with white matter lesions and atrophy on MRI occurs in carriers of this premutation and has recently been described as the fragile-X-associated tremor/ataxia syndrome. Recognition of this clinical picture is important for the patient but also for the relatives, since female carriers of the premutation have an increased risk of offspring with the fragile-X syndrome.

Timing of aneurysm surgery in subarachnoid haemorrhage--an observational study in The Netherlands.

BACKGROUND: There is still lack of evidence on the optimal timing of surgery in patients with aneurysmal subarachnoid haemorrhage. Only one randomised clinical trial has been done, which showed no difference between early and late surgery. Other studies were observational in nature and most had methodological drawbacks that preclude clinically meaningful conclusions. We performed a retrospective observational study on the timing of aneurysm surgery in The Netherlands over a two-year period. METHOD: In eight hospitals we identified 1,500 patients with an aneurysmal subarachnoid haemorrhage. They were subjected to predefined inclusion criteria. We included all patients who were admitted and were conscious at any one time between admission and the end of the third day after the haemorrhage. We categorised the clinical condition on admission according the World Federation of Neurological Surgeons (WFNS) grading scale. Early aneurysm surgery was defined as operation performed within three days after onset of subarachnoid haemorrhage; intermediate surgery as performed on days four to seven, and late surgery as performed after day seven. Outcome was classified as the proportion of patients with poor outcome (death or dependent) two to four months after onset of subarachnoid haemorrhage. We calculated crude odds ratios with late surgery as reference. We distinguished between management results (reconstructed intention to treat analysis) and surgical results (on treatment analysis). The results were adjusted for the major prognosticators for outcome after subarachnoid haemorrhage. FINDINGS: We included 411 patients. There were 276 patients in the early surgery group, 36 in the intermediate surgery group and 99 in the late surgery group. On admission 78% were in good neurological condition (WFNS I-III). MANAGEMENT RESULTS: Overall, 93 patients (34%) operated on early had a poor outcome, 13 (36%) of those with intermediate surgery and 37 (37%) in the late surgery group had a poor outcome. For patients in good clinical condition on admission and planned for early surgery the adjusted odds ratio (OR) was 1.3 (95% CI 0.5 to 3.0). The adjusted OR for patients admitted in poor neurologicalcondition (WFNS IV-V) and planned for early surgery was 0.1 (95% CI 0.0 to 0.6). SURGICAL RESULTS: For patients in good clinical condition on admission who underwent early operation the adjusted OR was 1.1 (95% CI 0.4 to 3.2); it was 0.2 (95% CI 0.0 to 0.9) for patients admitted in poor clinical condition. CONCLUSIONS: In this observational study we found no significant difference in outcome between early and late operation for patients in good clinical condition on admission. For patients in poor clinical condition on admission outcome was significantly better after early surgery. The optimal timing of surgery is not yet settled. Ideally, evidence on this issue should come from a randomised clinical trial. However, such a trial or even a prospective study are unlikely to be ever performed because of the rapid development of endovascular coiling.

Unilateral pallidotomy versus bilateral subthalamic nucleus stimulation in PD: a randomized trial.

OBJECTIVE: To compare the efficacy of unilateral pallidotomy and bilateral subthalamic nucleus (STN) stimulation in patients with advanced Parkinson disease (PD) in a randomized, observer-blind, multicenter trial. METHODS: Thirty-four patients with advanced PD were randomly assigned to have unilateral pallidotomy or bilateral STN stimulation. The primary outcome was the change from baseline to 6 months in the motor part of the Unified PD Rating Scale (motor UPDRS) in the off phase. Secondary outcomes were parkinsonian symptoms in the on phase (motor UPDRS), dyskinesias (Clinical Dyskinesia Rating Scale and dyskinesias UPDRS), functional status (activities of daily living UPDRS and Schwab and England scale), PD Quality of Life questionnaire, changes in drug treatment, and adverse effects. RESULTS: The off phase motor UPDRS score improved from 46.5 to 37 points in the group of pallidotomy patients and from 51.5 to 26.5 in the STN stimulation patients (p = 0.002). Of the secondary outcome measures, on phase motor UPDRS and dyskinesias UPDRS improved significantly in favor of the STN stimulation patients. Reduction of antiparkinsonian drugs was greater after STN stimulation than after pallidotomy. One patient in each group had a major adverse effect. CONCLUSIONS: Bilateral STN stimulation is more effective than unilateral pallidotomy in reducing parkinsonian symptoms in patients with advanced PD.

Endovascular coiling versus neurosurgical clipping in patients with a ruptured basilar tip aneurysm.

OBJECTIVES: To compare endovascular coiling with neurosurgical clipping of ruptured basilar bifurcation aneurysms. METHODS: Patient and aneurysm characteristics, procedural complications, and clinical and anatomical results were compared retrospectively in 44 coiled patients and 44 patients treated by clipping. The odds ratios for poor outcome (Glasgow outcome scale 1, 2, 3) adjusted for age, clinical condition, and aneurysm size were assessed by logistic regression analysis. RESULTS: In the endovascular group, five patients (11%) had a poor outcome v 13 (30%) in the surgical group; the adjusted odds ratio for poor outcome after coiling v clipping was 0.28 (95% confidence interval, 0.08 to 0.99). Procedural complications were more common in the surgical group. Optimal or suboptimal occlusion of the aneurysm immediately after coiling was achieved in 41 patients (93%). Clipping was successful in 40 patients (91%). CONCLUSIONS: The results suggest that embolisation with coils is the preferred treatment for patients with ruptured basilar bifurcation aneurysms.

Creutzfeldt-Jakob disease 38 years after diagnostic use of human growth hormone.

A 47 year old man is described who developed pathology proven Creutzfeldt-Jakob disease (CJD) 38 years after receiving a low dose of human derived growth hormone (hGH) as part of a diagnostic procedure. The patient presented with a cerebellar syndrome, which is compatible with iatrogenic CJD. This is the longest incubation period described so far for iatrogenic CJD. Furthermore, this is the first report of CJD after diagnostic use of hGH. Since the patient was one of the first in the world to receive hGH, other cases of iatrogenic CJD can be expected in the coming years.

Migraine with aura after intracranial endovascular procedures.

OBJECTIVE: To describe three cases of migraine (two with aura) after an intracranial endovascular procedure. Method.-Retrospective. RESULTS: One patient had an attack of migraine with prolonged aura after embolization of a dural arteriovenous fistula. Another patient had an attack of migraine with aura (and hemiparesis) after a diagnostic angiogram. The third patient already suffered from migraine with aura and had a migraine attack after embolization of an occipital arteriovenous malformation. A quadrantanopia persisted in this patient. Outcome of the other two patients was good. CONCLUSION: Intracranial endovascular procedures can induce migraine with aura. We could not identify the underlying pathophysiological mechanism, but mechanical, chemical, immunological, or hemodynamic factors could be involved.

Rupture of intracranial aneurysms during treatment with Guglielmi detachable coils: incidence, outcome, and risk factors.

OBJECT: The aim of this study was to assess the incidence and outcome of procedure-related rupture of intracranial aneurysms in patients treated with Guglielmi detachable coils (GDCs) and to identify risk factors for this complication. METHODS: Procedure-related rupture occurred in seven of 264 treated aneurysms in 239 consecutive patients. Aneurysm size, history of previous subarachnoid hemorrhage (SAH) caused by the treated aneurysm, timing of treatment after SAH, and the use of a temporary occlusion balloon in the seven procedures in which rupture occurred were compared with the remaining 257 procedures, and these findings were correlated with data from 13 studies in the literature, in which results of 2030 aneurysm treatments were reported. CONCLUSIONS: Procedure-related rupture of intracranial aneurysms during GDC treatment occurs in 2.5% of cases and is responsible for 1% of treatment-related deaths. Risk factors are as follows: small aneurysm size, previous SAH, and probably the use of a temporary occlusion balloon.

[Neuroradiologic intervention in two patients with cerebral sinus thrombosis]. / Neuroradiologische interventie bij 2 patiënten met cerebralesinustrombose.

Two patients with cerebral sinus thrombosis were successfully treated with neuroradiological intervention procedures, one with local thrombolysis and the other with mechanical thrombosuction using a hydrolyser catheter. The first patient, a 20-year-old woman, was treated with asparaginase for acute lymphatic leukaemia. She lapsed into coma with extensor posturing due to superior sagittal and right transverse sinus thrombosis. She recovered completely after local thrombolysis with 2,940,000 units urokinase, administered over a period of 40 hours. The second patient was a 29-year-old man who presented with clinical deterioration after seizures due to superior sagittal, left transverse and straight sinus thrombosis. A CT-scan demonstrated bilateral haemorrhagic cerebral infarctions. Since the risk of haemorrhage during thrombolysis with urokinase was considered to be high, mechanical thrombosuction with a hydrolyser catheter was performed. This procedure took only 4 hours. The patient recovered completely in two weeks. These cases add further evidence to the effectiveness of thrombolysis and thrombosuction in selected patients with severe cerebral sinus thrombosis.

Carotid balloon occlusion for large and giant aneurysms: evaluation of a new test occlusion protocol.

OBJECTIVE: Validation of a new angiographic test occlusion protocol before carotid balloon occlusion in patients with carotid aneurysms. METHODS: Carotid occlusion was considered for 29 consecutive patients. From 1993 to 1995, test occlusion in four patients consisted of clinical observation for 30 minutes and during electroencephalographic registration. From 1996 onward, test occlusion in 25 patients consisted of clinical observation and angiography of collateral vessels. Permanent balloon occlusion was performed only when the cortical veins in both the occluded and the collateral vascular territories filled synchronously. RESULTS: Two of the four patients with normal clinical and electroencephalographic findings during test occlusion developed delayed hypoperfusion infarction after permanent carotid occlusion. Seventeen of 25 patients (68%) demonstrated both clinical and angiographic tolerance, and no ischemic events occurred after permanent carotid occlusion. In one patient with clinical tolerance but angiographic nontolerance, permanent carotid occlusion had to be performed, which resulted in delayed hypoperfusion infarction. In two patients with angiographic nontolerance, venous filling became synchronous after bypass surgery. Long-term clinical follow-up showed an alleviation of the symptoms of mass effect in 14 of 21 patients (67%). Magnetic resonance imaging follow-up (range, 3-70 mo) revealed a reduction in the size of the aneurysm in 19 of 21 patients (90%). CONCLUSION: Test occlusion with clinical and angiographic control is reliable, safe, and simple to perform.

Unilateral pallidotomy in Parkinson's disease: a randomised, single-blind, multicentre trial.

BACKGROUND: The results of several cohort studies suggest that patients with advanced Parkinson's disease would benefit from unilateral pallidotomy. We have assessed the efficacy of unilateral pallidotomy in a randomised, single-blind, multicentre trial. METHODS: We enrolled 37 patients with advanced Parkinson's disease who had, despite optimum pharmacological treatment, at least one of the following symptoms: severe response fluctuations, dyskinesias, painful dystonias, or bradykinesia. Patients were randomly assigned to unilateral pallidotomy within 1 month or to pallidotomy after the primary outcome assessment (6 months later). The primary outcome was the difference between the groups in median changes on the motor examination section of the unified Parkinson's disease rating scale (UPDRS 3) score done in the off phase. Secondary outcome measures included levodopa-induced dyskinesias (dyskinesia rating scale [DRS]) and extent of disability (UPDRS 2). FINDINGS: The median UPDRS 3 off score of the pallidotomy patients improved from 47 to 32.5, whereas that of control patients slightly worsened from 52.5 to 56.5 (p<0.001). In the on phase the median DRS score improved 50% in pallidotomy patients compared with no change in controls. The UPDRS 2 off score improved with a median of 7 in the pallidotomy group. Two treated patients had major adverse effects. INTERPRETATION: Unilateral pallidotomy is an effective treatment in patients with advanced Parkinson's disease, who have an unsatisfactory response to pharmacological treatment.

Alpha rhythms: noise, dynamics and models.

Alpha rhythms appear as sinusoidal-like oscillations in the electroencephalogram (EEG) within the frequency range 8-12 Hz that waxe and wane in a more or less irregular way. The irregularity may have various origins. It may be due to noise or the oscillations may have an intrinsic irregular character, e.g. they may be generated by chaotic processes [Jansen (1991) Quantitative analysis of electroencephalograms: is there chaos in the future? Int. J. Biomed. Comput., 27: 95-123; Pradham, N. and Dutt, D.N. (1993) A nonlinear perspective in understanding the neurodynamics of EEG. Comput. Biol. Med., 23: 425-442; Pritchard et al. (1995) Dimensional analysis of resting human EEG II: Surrogate-data testing indicates nonlinearily but not low-dimensional chaos. Psychophysiology. 32: 486]. The term noise is often used in neurophysiology with different connotations as pointed out by Bullock (1990), either meaning an unwanted signal from the point of view of the receiver of a message, or a signal with intrinsic random fluctuations, i.e. with a stochastic character. Here we consider noise in this sense, as random or quasi-random neural activity. In this overview, we concentrate on the question of whether alpha rhythms should be considered generated in neuronal networks (1) as forms of filtered noise, (2) as deterministic oscillations influenced by noise or (3) as the result of chaotic dynamics. A clear answer to this question can have theoretical value because it may lead to a general model of the generation of this important EEG signal. Such a model, of course, would be a macroscopic one, since it would primarily account for the properties of the alpha rhythms at the neuronal network level. A translation of these properties to the microscopic, i.e. neuronal, level will not be easy to achieve without more direct knowledge of the membrane and synaptic basic properties of the neurons involved. Here we consider the question formulated above by presenting some relevant experimental evidence and theoretical arguments. The consideration whether alpha rhythms may have noise or chaotic sources implies examining how and where such sources can occur in the neuronal networks of the brain. Therefore we present, first, some basic data regarding the possible origin of noise and of chaos in neuronal networks. Second, the signal analysis methods that have to be applied in order to discriminate between filtered noise activities and chaotic oscillations are introduced. Third, the implications of these signal analyses regarding the possible answer to the initial question are discussed.

Familial anaplastic ependymoma: evidence of loss of chromosome 22 in tumour cells.

A family with anaplastic ependymomas, histologically verified in three cases and neuroradiologically suggested in a fourth, is presented. Two healthy brothers both had two affected sons. All four male patients were younger than 5 years at the time of diagnosis. Two boys died before the age of 3 years. Genotype analysis (with polymorphic DNA markers for chromosome 22 and interphase cytogenetic analysis) of one of the tumours showed a subpopulation of tumour cells with monosomy of (part of) chromosome 22. Non-neoplastic cells of this patient showed a normal karyotype. These findings give further evidence for the role of a tumour suppressor gene on chromosome 22 in the pathogenesis of familial ependymal tumours.

Opioid-inhibited adenylyl cyclase in rat brain membranes: lack of correlation with high-affinity opioid receptor binding sites.

Opioid agonists bind to GTP-binding (G-protein)-coupled receptors to inhibit adenylyl cyclase. To explore the relationship between opioid receptor binding sites and opioid-inhibited adenylyl cyclase, membranes from rat striatum were incubated with agents that block opioid receptor binding. These agents included irreversible opioid agonists (oxymorphone-p-nitrophenylhydrazone), irreversible antagonists [naloxonazine, beta-funaltrexamine, and beta-chlornaltrexamine (beta-CNA)], and phospholipase A2. After preincubation with these agents, the same membranes were assayed for high-affinity opioid receptor binding [3H-labeled D-alanine-4-N-methylphenylalanine-5-glycine-ol-enkephalin (mu), 3H-labeled 2-D-serine-5-L-leucine-6-L-threonine enkephalin (delta), and [3H]ethylketocylazocine (EKC) sites] and opioid-inhibited adenylyl cyclase. Although most agents produced persistent blockade in binding of ligands to high-affinity mu, delta, and EKC sites, no change in opioid-inhibited adenylyl cyclase was detected. In most treated membranes, both the IC50 and the maximal inhibition of adenylyl cyclase by opioid agonists were identical to values in untreated membranes. Only beta-CNA blocked opioid-inhibited adenylyl cyclase by decreasing maximal inhibition and increasing the IC50 of opioid agonists. This effect of beta-CNA was not due to nonspecific interactions with G(i), Gs, or the catalytic unit of adenylyl cyclase, as neither guanylylimidodiphosphate-inhibited, NaF-stimulated, nor forskolin-stimulated activity was altered by beta-CNA pretreatment. Phospholipase A2 decreased opioid-inhibited adenylyl cyclase only when the enzyme was incubated with brain membranes in the presence of NaCl and GTP. These results confirm that the receptors that inhibit adenylyl cyclase in brain do not correspond to the high-affinity mu, delta, or EKC sites identified in brain by traditional binding studies.