Effect of selective dorsal rhizotomy on daily care and comfort in non-walking children and adolescents with severe spasticity.

BACKGROUND: In non-walking children with severe spasticity, daily care can be difficult and many patients suffer from pain. Selective dorsal rhizotomy (SDR) reduces spasticity in the legs, and therefore has the potential to improve daily care and comfort. AIM: To examine effects of SDR on daily care and comfort in non-walking children with severe spasticity due to different underlying neurological conditions. METHODS: Medical history, changes in daily care and comfort and satisfaction with outcome were assessed retrospectively in non-walking children who underwent SDR in our center, with a mean follow-up of 1y 7m (range 11m-4y 3m). All eligible patients (n = 24, years 2009-2014) were included. RESULTS: Mean age at SDR was 12y 4m (SD 4y 3m, range 2y 8m-19y 3m). Associated orthopaedic problems were frequent. Seven patients underwent scoliosis correction in the same session. Most improvements were reported in dressing (n = 16), washing (n = 12) and comfort (n = 10). Median score for satisfaction was 7 on a scale of 10 (range 1-9). SDR resulted in reduction of spasticity in leg muscles. In nine patients dystonia was recorded post-operatively, mainly in children with congenital malformations and syndromes. INTERPRETATION: SDR is a single event intervention that can improve daily care and comfort in non-walking children with severe spasticity, and can safely be combined with scoliosis correction. Despite the improvements, satisfaction is variable. Careful attention is necessary for risk factors for dystonia, which may be unmasked after SDR.

Feasibility of online seizure detection with continuous EEG monitoring in the intensive care unit.

INTRODUCTION: Continuous EEG (cEEG) is of great interest in view of the reported high prevalence of non-convulsive seizures on intensive care units (ICUs). Here, we describe our experiences applying a seizure warning system using cEEG monitoring. METHODS: Fifty comatose ICU patients were included prospectively and monitored. Twenty-eight patients had post-anoxic encephalopathy (PAE) and 22 had focal brain lesions. A measure of neuronal interactions, synchronization likelihood, was calculated online over 10s EEG epochs and instances when the synchronization likelihood exceeded a threshold where marked as seizures. RESULTS: Five patients developed seizures. Our method detected seizures in three patients, in the other patients seizures were missed because of they were non-convulsive and had a focal character. The average false positive rate was 0.676/h. DISCUSSION: This is our first attempt to implement online seizure detection in the ICU. Despite problems with artifacts and that we missed focally oriented seizures, we succeeded in monitoring patients online. Given the relatively high occurrence of seizures, online seizure detection with cEEG merits further development for use in ICUs.

Motor evoked potential: a reliable and objective measure to document the functional consequences of multiple sclerosis? Relation to disability and MRI.

OBJECTIVE: In an attempt to analyze whether MEP can serve as a valid measure for evaluating neurological dysfunction in multiple sclerosis (MS), we related MEP to clinical and MRI measures. METHODS: Transcranial magnetic stimulation was applied in 52 MS patients to determine the central motor conduction time (CMCT) to the extremities. We calculated Z-scores for each CMCT (Zcmct) corrected for height. All patients underwent two clinical measurements and a MRI scan, of which T1 and T2 brain lesion volumes, brain volume, spinal cord volume and the number of T2 spinal cord lesions were derived. RESULTS: The clinical measurements correlated significantly with various Zcmct (Spearman correlation coefficients ranged from 0.29 to 0.53; p<0.05). The number of spinal cord lesions, brain T1 and T2 lesion volume and spinal cord volume correlated with various Zcmct (r=0.31-0.53; p<0.05). Linear regression analysis revealed that the clinical measurements were explained by Zcmct left leg and T1 lesion volume (adjusted R(2)=0.38). For one clinical measurement the number of spinal cord lesions was also included (adjusted R(2)=0.43). CONCLUSION: We found a relation between MEP, brain and spinal cord MRI measures, and two clinical measures. Moreover, a model for explaining disability in MS revealed that MEP measures provide information in addition to MRI measures. SIGNIFICANCE: This study suggests that MEP is a measure that might adequately reflect pathology and neurological dysfunction in MS.

Neonatal seizure monitoring using non-linear EEG analysis.

Birth asphyxia is a major concern in neonatal care. Epileptic seizures are associated with subsequent neurodevelopmental deficits. Eighty-five percent of these seizures remain subclinical and therefore an on-line monitoring device is needed. In an earlier study we showed that the synchronization likelihood was able to distinguish between neonatal EEG epochs with and without epileptic seizures. In this study we investigated whether the synchronization likelihood can be used in complete EEGs, without artifact removal. Twenty complete EEGs from 20 neonatal patients were studied. The synchronization likelihood was calculated and correlated with the visual scoring done by 3 experts. In addition, we determined the influence of seizure length on the likelihood of detection. Using the raw unfiltered EEG data we found a sensitivity of 65.9 % and a specificity of 89.8 % for the detection of seizure activity in each epoch. In addition, the seizure detection rate was 100 % when the seizures lasted for 100 seconds or more. The synchronization likelihood seems to be a useful tool in the automatic monitoring of epileptic seizures in infants on the neonatal ward. Due to the retrospective nature of our study, the consequences for clinical intervention cannot yet be determined and prospective studies are needed. Therefore, we will conduct a prospective study on the neonatal intensive care unit with a recently developed on-line version of the synchronization likelihood analysis.

Predictive value of EEG in neonates with periventricular leukomalacia.

The aim of this study was to evaluate whether EEG (i.e. positive Rolandic sharp waves) can be used to predict neurodevelopment in newborn infants with periventricular leukomalacia and compare the predictive value with that of MRI. A sequential cohort of neonates (n=45; 33 males, 12 females; mean gestational age 31.2 weeks, SD 2.7, range 27 to 37.8 weeks; mean birthweight 1592 g, SD 601 g) with periventricular hyperechogenicities on cranial ultrasound was recruited for this study. EEGs were analyzed for positive Rolandic sharp waves. Neurodevelopment was evaluated at the ages of 12 and 18 months. In the whole group the probability of a poor outcome was 24% and the probability of any impairment was 33%. If the number of positive Rolandic sharp waves was no more than 0.1 per minute, the probability of a poor outcome was reduced to 9% (95% confidence interval [95%CI] 2 to 27%) and the probability of any impairment was reduced to 13% (95%CI 4 to 32%). In all infants with more than 0.1 positive Rolandic sharp waves per minute the probability of a poor outcome was 41% (95%CI 23 to 61%) and of any impairment was 55% (95%CI 34 to 73%). In these infants MRI identified infants with a poor outcome with a sensitivity of 1.00 (95%CI 0.70 to 1.00) and a specificity of 0.92 (95%CI 0.67 to 0.99), and infants with any impairment with a sensitivity of 0.83 (95%CI 0.55 to 0.95) and a specificity of 1.00 (95%CI 0.72 to 1.00). Results suggest that if an EEG of an infant with periventricular leukomalacia contains no more than 0.1 positive Rolandic sharp waves per minute the probability of a normal or mildly delayed development is high (0.91, 95%CI 0.73 to 0.98). MRI enhances the accuracy of the outcome prediction slightly; however, owing to a wide confidence interval, this advantage is negligible. However, if the frequency of the positive Rolandic sharp waves exceeds 0.1per minute, MRI can significantly enhance the precision of the prediction of outcome.

Dynamics of the pituitary-adrenal ensemble in hypocretin-deficient narcoleptic humans: blunted basal adrenocorticotropin release and evidence for normal time-keeping by the master pacemaker.

Narcolepsy is a sleep disorder caused by disruption of hypocretin (orexin) neurotransmission. It has been suggested that anomalous timing by the biological clock contributes to the symptomatology. Hypocretins stimulate the pituitary-adrenal (PA) axis in rodents. We explored whether hypocretin deficiency disrupts circadian timing and blunts PA hormone release. We deconvolved 24-h plasma profiles of ACTH and cortisol, and determined their circadian rhythm by cosinor analysis in seven hypocretin-deficient narcoleptic males and seven matched controls. Basal and total ACTH production were blunted in narcoleptics [310 +/- 86 vs. 760 +/-160 ng/liter.24 h (P = 0.02) and 920 +/- 147 vs. 1460 +/- 220 ng/liter.24 h (P = 0.04), respectively], whereas pulsatile release did not differ between groups. In contrast, basal, pulsatile and total cortisol secretion were similar in both groups. The cross-approximate entropy of the joint ACTH/cortisol time series was higher in narcoleptics (1.26 +/- 0.07 vs. 1.07 +/- 0.04; P = 0.04), reflecting reduced secretory process regularity. The acrophases of both ACTH and cortisol occurred at similar clock times (approximately 0830 h) in patients and controls, which supports the idea that the master pacemaker is intact in narcolepsy. The reduced (basal) ACTH secretion and the diminished secretory process regularity of the ACTH/cortisol ensemble conjointly suggest that hypocretin deficiency induces changes in the interplay between PA hormones.

Nonlinear EEG analysis in early Alzheimer's disease.

Nonlinear EEG analysis attempts to characterize the dynamics of neural networks in the brain. Abnormalities in nonlinear EEG measures have been found repeatedly in Alzheimer's disease (AD). The present study was undertaken to investigate whether these abnormalities could already be found in the early stage of AD. In a representative sample of 49 community-dwelling elderly, Alzheimer's disease was diagnosed in 7 subjects. Correlation dimension (D2) and nonlinear prediction were measured at 16 electrodes and in two different activational states. Also, 10 surrogate data sets were generated for each EEG epoch in order to investigate the presence of nonlinear dynamics. Differences between nonlinear statistics derived from original and from surrogate data sets were expressed as Z-scores. We found lower D2 and higher predictability in the demented subjects compared to the normal subjects. The results obtained with the Z-scores pointed to changed nonlinear dynamics in frontal and temporal areas in demented subjects. However, the major differences between demented and healthy subjects are not due to nonlinearity. From this it appears that linear dynamics change first in the course of AD, followed by changes in nonlinear dynamics.

The diagnostic value of electroencephalography in mild senile Alzheimer's disease.

OBJECTIVE: We investigated the diagnostic value of the visually assessed electroencephalogram (EEG) in patients with mild Alzheimer's disease (AD), using the grand total of EEG (GTE) score. METHODS: Forty-nine non-demented control subjects with and without minimal cognitive impairment from the general population and 86 probable AD patients (NINCDS-ADRDA criteria), consecutively referred to a memory clinic, participated in this study. RESULTS: Frequency of rhythmic background activity (P<0.05), diffuse slow activity (P<0.001), and reactivity of the rhythmic background activity (P<0.001) were statistically significant related to the diagnosis control subject or AD patient, using logistic regression analysis with adjustment for age and sex. When these subscores were used to confirm the diagnosis of AD, thus at high specificity of 89.1% (GTE cut-off point of 3), the sensitivity was 44.6% and positive predictive value was 88.1%. Incremental ruling-in and ruling-out curves showed a maximum diagnostic gain of 38% for a positive test result at a prior probability ranging from 30 to 40%. At high pretest probability levels of 80-90%, the diagnostic gain for a positive test result was low, varying from 7 to 14%. CONCLUSION: In conclusion, the visually assessed EEG may give a clinically meaningful contribution to the diagnostic evaluation of AD when there is diagnostic doubt.

Third-degree obstetric perineal tear: long-term clinical and functional results after primary repair.

BACKGROUND: This study was designed to investigate the long-term clinical and anorectal functional results after primary repair of a third-degree obstetrical perineal rupture. METHODS: One hundred and fifty-six consecutive women who had a primary repair of a third-degree perineal rupture were sent a questionnaire and asked to undergo anorectal function testing (anal manometry, anorectal sensitivity, anal endosonography and pudendal nerve terminal motor latency (PNTML)) RESULTS: Some 117 women (75 per cent) responded. Anal incontinence was present in 47 women (40 per cent); however, in most cases only mild symptoms were present. In 40 women additional anorectal function tests were performed and compared with findings in normal controls. Mean(s.d.) maximum squeeze pressure (31(15) versus 63(17) mmHg, P< 0.001) was decreased and first sensation to filling of the rectum (88(47) versus 66(33) ml, P=0.03) and anal mucosal electrosensitivity (4.7(1.7) versus 2.5(0.8) mA, P=0.003) were increased compared with values in normal controls. In 35 women (88 per cent) a sphincter defect was found with anal endosonography. Factors related to anal incontinence were the presence of a combined anal sphincter defect (relative risk (RR) 1.7 (95 per cent confidence interval (c.i.) 1.1-2.8)) or subsequent vaginal delivery (RR 1.6 (95 per cent c.i. 1.1-2.5)). CONCLUSION: Anal incontinence prevails in 40 per cent of women 5 years after primary repair of a third-degree perineal rupture. The presence of a combined sphincter defect or subsequent vaginal delivery increase the risk of anal incontinence.

Reproducibility of different methods for diagnosing and monitoring diabetic neuropathy.

Conflicting results have been published concerning the reliability of methods to assess diabetic polyneuropathy. Therefore we compared the reproducibility of nerve conduction studies and quantitative measurements of vibratory sensation in 23 diabetic patients with clinically and/or neurophysiologically established neuropathy. Motor nerve conduction of peroneal and median nerves, sensory nerve conduction of sural and median nerves and vibratory perception thresholds of index fingers and big toes (forced-choice method) were assessed on three occasions with an interval of one to fourteen days, within a period of three weeks. We conclude that both nerve conduction studies and vibratory perception threshold measurements are reproducible methods to assess diabetic neuropathy. Determination of vibration perception thresholds has the advantage of being a simple and unobtrusive method. Nerve conduction studies are less variable and therefore more suited for monitoring diabetic neuropathy.

Diagnosing Alzheimer's disease in community-dwelling elderly: a comparison of EEG and MRI.

In a study on the course of cognitive impairment in people over 65 years of age, 58 randomly selected community dwelling elderly underwent EEG and MRI studies. The EEG was visually and quantitatively (qEEG) assessed. Nine out of 58 subjects appeared to have Alzheimer dementia (AD) according to CAMDEX criteria. In this group medial temporal lobe atrophy on MRI, as an objective criterium for AD, showed a total accuracy of 72%, visually assessed EEG 81% and qEEG 81-84%. There was an incomplete overlap in subjects regarding MRI and EEG abnormalities, implying that both methods may be complementary.

Measurement of patellar and ankle tendon reflexes in normal subjects.

In order to acquire normal values, patellar and ankle tendon reflexes were measured bilateral in 51 healthy subjects. The reflexes were mechanically evoked with a hand-held hammer which was connected to the trigger input of a two-channel EMG system. For each reflex simultaneous registration took place from surface electrodes on two different locations. The dependence of the latency on body length and age is described as well as the left-right difference and the intra-individual variability. Using similar measurement conditions significantly longer latencies were found than those published earlier. The importance of well defined placement of the electrodes when comparing acquired latencies with normal values is shown.

Unsuspected sphincter defects shown by anal endosonography after anorectal surgery. A prospective study.

PURPOSE: Anorectal surgery can lead to fecal soiling and incontinence. Whether surgery changes the anatomy and causes symptoms is unknown. Anatomic changes can be visualized by anal endosonography. METHODS: We studied 50 patients after hemorrhoidectomy (24), fistulectomy (18), and internal sphincterotomy (8). Symptoms were assessed, and anal endosonography, anal manometry, mucosal electrosensitivity, and neurophysiologic tests were performed. RESULTS: In 23 (46 percent) patients, a defect of the anal sphincter was found (13 patients had an internal sphincter defect, 1 had an external sphincter defect, and 9 had a combined sphincter defect), 3 after hemorrhoidectomy, 13 after fistulectomy, and 7 after internal sphincterotomy. Seven patients had symptoms, and they all had a sphincter defect. In the other 16 of 23 patients (70 percent), the sphincter defect did not produce symptoms. An internal sphincter defect lowered maximum basal pressure and shortened sphincter length. CONCLUSION: Anal endosonography can reveal sphincter defects after anorectal surgery. Seventy percent of the patients in this group had no complaints; therefore, defects were unsuspected. This has clinical implications in the evaluation of patients with fecal incontinence.

Fatigue, sleep disturbances and circadian rhythm in multiple sclerosis.

The aim of this study was to investigate whether fatigue and sleep disturbances in multiple sclerosis (MS) patients might be due to disrupted circadian sleep wake regulation. Actigraphy and a multiple sleep latency test (MSLT) were performed in 16 MS patients with both prominent sleep complaints and fatigue. Actigraphy scores did not differ from control values, whereas sleep onset latency values were altered in subgroups of MS patients. No evidence was found for a generalized circadian disturbance in MS patients.

4-Aminopyridine induces functional improvement in multiple sclerosis patients: a neurophysiological study.

This study reports on the neurophysiological measurements that were performed in the context of a randomized, double-blind, placebo-controlled, cross-over study with intravenously administered 4-aminopyridine (4-AP) in 70 patients with definite multiple sclerosis (MS). A beneficial effect of 4-AP was found for both visual evoked response and eye movement registration parameters. This study extends the experimental data obtained on animal nerve fibers, showing that 4-AP can improve impulse conduction in demyelinated nerve, to clinical data which indicate that 4-AP induces an objective improvement in the central nervous system function in MS-patients. It thereby also provides a theoretical basis for clinical efficacy of 4-AP in MS.

Clinical examination versus neurophysiological examination in the diagnosis of diabetic polyneuropathy.

Several methods have been used to diagnose diabetic polyneuropathy and to quantitate the degree of affection of peripheral nerves. Using a newly developed scoring system we compared bedside clinical examination with neurophysiological examination in a group of 78 diabetic patients. Individual scores for clinical examination were significantly correlated with scores for neurophysiological examination (r = 0.7, p < 0.0005). All 78 patients had at least one clinical symptom or sign of polyneuropathy. Clinical examination indicated polyneuropathy in three patients with neuropathic complaints, while neurophysiological examination in these patients showed no abnormalities. In 12 out of 14 patients with normal neurophysiological sensory nerve function, clinical examination showed at least one abnormal sensory modality. Comparing the four different sensory modalities, light touch sense and pinprick sense indicated polyneuropathy better than vibration or position senses. An abnormal Hoffmann reflex of the soleus muscle was always associated with a decreased or absent ankle jerk. The scoring system for the clinical examination proved useful for diagnosing and quantitating the severity of diabetic polyneuropathy. Clinical sensory deficits could not be inferred from the results of neurophysiological testing of sensory nerve function. Pinprick sense, light touch sense, and ankle jerks were the most important parameters in the clinical diagnosis of diabetic polyneuropathy.

Anal endosonography: relationship with anal manometry and neurophysiologic tests.

Thirty-seven patients were referred for evaluation of anal function; their clinical diagnoses were traumatic fecal incontinence (13), idiopathic (pudendal neuropathy) fecal incontinence (7), fecal soiling (9), and other (8). In all patients, anal endosonography (sphincter defects and internal sphincter thickness [IST]) and anal manometry (maximal basal pressure [MBP] and maximal squeeze pressure [MSP]) were performed. In 18 patients, neurophysiologic tests (EMG-maximal contraction pattern [MCP], single-fiber EMG [fiber density; FD], and pudendal nerve terminal motor latency [PNTML]) were also performed. Endosonography demonstrated in seven patients both an internal and external sphincter defect (Group 1), in seven patients an internal sphincter defect and in one patient an external sphincter defect (Group 2), and in 22 patients no sphincter defect (Group 3). There was a significant difference among these three groups for MBP and MCP, the lowest being in Group 1. Between the patients with traumatic fecal incontinence and idiopathic fecal incontinence, no differences in IST, MBP, MSP, MCP, FD, and PNTML were found. In two patients with a suspected obstetric trauma, there was an unexpected additional severe pudendal neuropathy. In one patient with a suspected obstetric trauma, no damage of the anal sphincters could be demonstrated. In one patient with suspected idiopathic fecal incontinence, there was an additional, unsuspected defect of the internal sphincter. There was concordance between endosonography and EMG in the mapping of the external sphincter. Clinical diagnoses can be misleading in differentiating between traumatic and idiopathic fecal incontinence; anal endosonography provides unsuspected and additional information about the sphincters; PNTML can reveal unsuspected neuropathy in traumatic fecal incontinence. Therefore, the combination of endosonography and PNTML is promising in selecting patients for surgery.

Evaluation of the visual system in multiple sclerosis: a comparative study of diagnostic tests.

In 22 patients with clinically definite multiple sclerosis (MS) who were without visual symptoms and had a visual acuity of at least 1.0 in both eyes at the time of measurement, the following tests were performed to detect subclinical lesions in the visual system: visual evoked potential (VEP), contrast sensitivity test (CS), flight of colours test (FOC), colour vision test (Ishihara plates) (CV) and the pupillary light reflex (PLR). VEP was abnormal in 81.8%, CS in 72.7%, FOC in 36.4%, CV in 31.8%, and PLR in 52.3% of the patients. VEP and CS together were most sensitive: combining these techniques subclinical lesions of the visual system were detected in 90.9% (20/22) of these asymptomatic patients.

Cyclandelate in diabetic neuropathy. A double-blind, placebo-controlled, randomized, cross-over study.

Cyclandelate has the ability to improve the rheological properties of the blood and therefore may improve blood supply of peripheral nerves. Previous studies in diabetic neuropathy have shown beneficial effects of the drug. We performed a double-blind, placebo-controlled, cross-over study in 40 diabetic patients with cyclandelate in a dose of 1600 mg daily. Motor and sensory nerve conduction velocities, late responses, thermal discrimination thresholds, vibration perception thresholds and pain scores were studied. We were not able to show any positive effect of the drug and therefore conclude that cyclandelate is not effective in the treatment of diabetic neuropathy.

The cause of increased pupillary light reflex latencies in diabetic patients: the relationship between pupillary light reflex and visual evoked potential latencies.

In 42 diabetic patients the relationship between the latency of the pupillary light reflex and the pattern reversal visual evoked potential (P100) was examined. Fifty-five percent of diabetic patients had pupillary light reflex latencies above the normal range. In 19% the visual evoked potentials were prolonged when compared to the normal range. Latencies of pupillary light reflexes and VEPs showed no correlation. There was a minimal correlation between the presence of retinopathy and prolongation of both the pupillary light reflex and the visual evoked response latency (kappa coefficients respectively: 0.31, P less than 0.01 and 0.36, P less than 0.02). The presence of an increased pupillary light reflex latency was positively correlated with a reduced respiratory sinus arrhythmia (kappa coefficient: 0.58, P less than 0.0001). Increased VEP latencies showed no correlation with signs of cardiovascular autonomic neuropathy. We conclude that the afferent optic pathway can be affected in diabetic patients. However, prolongation of pupillary light reflex latency in diabetic patients is primarily due to an efferent pupillary defect and represents parasympathetic dysfunction.