Clinical Features of Neuromuscular Disorders in Patients with N-Type Voltage-Gated Calcium Channel Antibodies.

Neuromuscular junction disorders affect the pre- or postsynaptic nerve to muscle transmission due to autoimmune antibodies. Members of the group like myasthenia gravis and Lambert-Eaton syndrome have pathophysiologically distinct characteristics. However, in practice, distinction may be difficult. We present a series of three patients with a myasthenic syndrome, dropped-head syndrome, bulbar and respiratory muscle weakness and positive testing for anti-N-type voltage-gated calcium channel antibodies. In two cases anti-acetylcholin receptor antibodies were elevated, anti-P/Q-type voltage-gated calcium channel antibodies were negative. All patients initially responded to pyridostigmine with a non-response in the course of the disease. While one patient recovered well after treatment with intravenous immunoglobulins, 3,4-diaminopyridine, steroids and later on immunosuppression with mycophenolate mofetil, a second died after restriction of treatment due to unfavorable cancer diagnosis, the third patient declined treatment. Although new antibodies causing neuromuscular disorders were discovered, clinical distinction has not yet been made. Our patients showed features of pre- and postsynaptic myasthenic syndrome as well as severe dropped-head syndrome and bulbar and axial muscle weakness, but only anti-N-type voltage-gated calcium channel antibodies were positive. When administered, one patient benefited from 3,4-diaminopyridine. We suggest that this overlap-syndrome should be considered especially in patients with assumed seronegative myasthenia gravis and lack of improvement under standard therapy.

Value of DSA in the diagnostic workup of pulsatile tinnitus.

OBJECTIVES: Pulsatile tinnitus (PT) is a rare complaint, but can be a symptom of life-threatening disease. It is often caused by vascular pathologies, e.g. dural arteriovenous fistula (dAVF), arteriovenous malformation (AVM) or vascularized tumors. The current diagnostic pathway includes clinical examination, cranial MRI and additional DSA. The aim of this study was to evaluate the diagnostic impact of DSA in the diagnostic workup of patients with PT in comparison to MRI alone. METHODS: Retrospectively, 54 consecutive patients with pulsatile tinnitus were evaluated. All patients had a diagnostic workup including cranial MRI and DSA. MRI examinations were blinded to the results of DSA and retrospectively analyzed in consensus by two experienced neuroradiologists. The MR-examinations were evaluated for each performed sequence separately: time-of-flight-angiography, ce-MRA, T2, ce-T1-sequence and ce-T1-sequence with fat saturation. RESULTS: 37 of the 54 patients revealed a pathology explaining PT on MRI, which was detected by the readers in 100% and proofed by means of DSA. 24 dAVF, four paraganglioma, two AVM and seven more pathologies were described. All patients without pathology on MRI did also not show any pathology in DSA. CONCLUSIONS: MR imaging is sufficient to exclude pathology in patients with pulsatile tinnitus.

Diagnostic value of 3D fluid attenuated inversion recovery sequence in multiple sclerosis.

BACKGROUND: Magnetic resonance imaging (MRI) is an indispensable tool in the diagnostic work-up of multiple sclerosis (MS). To date, guidelines suggest MRI protocols containing axial dual-echo, unenhanced and post-contrast T1-weighted sequences. Especially the usage of dual-echo sequences has markedly improved the ability of MRI to detect cortical and infratentorial lesions. Newer 3D FLAIR sequences are supposed to provide even more positive imaging features such as improved detection of white matter lesions and a better resolution due to smaller slice thickness. PURPOSE: To evaluate the diagnostic impact of 3D FLAIR sequences in comparison to conventional T2 and PD sequences. MATERIAL AND METHODS: Examinations of 20 MS patients (10 women, 10 men) were reviewed retrospectively. All patients received MRI standard protocol containing PD and T2 sequences and a mid-sagittal T2 sequence. Additionally an isotropic 3D FLAIR sequence was performed. Whole-brain lesion load and number of lesions in juxtacortical, infratentorial, and midcallosal localizations were assessed by two observers independently and compared. RESULTS: Whole lesion load and the count of detectable lesions at the 3D FLAIR sequence were significantly higher in the juxtacortical and infratentorial regions compared to the PD/T2 sequence. Detection rate of midcallosal lesions did not differ significantly in sagittal T2 and 3D FLAIR sequence. CONCLUSION: 3D FLAIR sequences can improve the detection of brain lesions in patients with MS and are even more sensitive in depicting lesions in cortical and infratentorial locations than current dual-echo sequences. The sequence can replace both PD/T2 sequences and mid-sagittal T2 sequences of the corpus callosum.

No evidence of jugular venous valve insufficiency in patients with migraine--a controlled study.

BACKGROUND: Migraine with aura is associated with patent foramen ovale and right-left-shunt. Jugular venous valve insufficiency is a further vascular anomaly. It is a frequent finding in transient global amnesia which is associated with migraine. Therefore, we investigated the prevalence of jugular venous valve insufficiency in migraine. METHODS: Subjects included in this study were participants of the population based German Headache Study on the prevalence of primary headaches. In 36 patients with migraine with aura, 50 patients with migraine without aura and 43 controls without headaches duration of backward venous flow, peak velocity flow and diameters of the jugular venous valves were assessed by color-coded duplex and Doppler sonography and compared between groups. In all migraine patients, examination was performed between and not during migraine attacks. Therefore, 9 additional patients with chronic daily headache were investigated during headache. RESULTS: We did not find statistically significant differences in duration of flow, peak velocity flow and diameter of the jugular venous valves in patients with migraine with aura (mean values 0.53 ± 0.43 sec; 35.47 ± 33.87 cm/sec; 8.84 ± 3.17 mm), migraine without aura (0.61 ± 0.63 sec; 33.39 ± 25.80 cm/sec; 8.15 ± 3.02 mm) or controls (0.64 ± 0.51 sec; 35.28 ± 31.76 cm/sec; 8.79 ± 2.97 mm) (group effects p-values >0.41). For all parameters results were the same for the left and the right side of jugular venae (side effects p-values >0.09). Also patients with chronic daily migraine with headache during the examination showed no differences to controls (0.52 ± 0.49 sec; 27.95 ± 21,75 cm/sec; 8.07 ± 2.71 mm) (all p-values > 0.23). CONCLUSIONS: The prevalence of internal jugular venous valve insufficiency is not increased in persons with migraine.

Pallidal deep brain stimulation relieves camptocormia in primary dystonia.

Camptocormia, characterised by a forward flexion of the thoracolumbar spine may occur in various movement disorders, mainly in Parkinson's disease or in primary dystonia. In severe cases, patients with camptocormia are unable to walk. While treatment options are limited, deep brain stimulation (DBS) with bilateral stimulation of the subthalamic nucleus or globus pallidus internus (GPi) has been proposed as a therapeutic option in refractory cases of Parkinson's disease. Here we present two patients with severe camptocormia as an isolated form of dystonia and as part of generalised dystonia, respectively, which were both treated with bilateral stimulation of the GPi. Symptoms of dystonia were assessed using the Burke-Fahn-Marsden dystonia rating scale (BFM) before and during deep brain stimulation. In both patients there was a significant functional improvement following long-term bilateral GPi stimulation and both patients gained ability to walk. In the first patient with an isolated dystonic camptocormia the BFM motor subscore for the truncal flexion improved by 75 %. The total BFM motor score in the second patient with a camptocormia in generalised dystonia improved by 45 %, while the BFM score for truncal flexion improved by 87 %. In both patients the effect of the bilateral GPi stimulation on camptocormia was substantial, independent of generalisation of dystonia. Therefore, GPi DBS is a possible treatment option for this rare disease.

Neuroform stent-assisted treatment of intracranial aneurysms: long-term follow-up study of aneurysm recurrence and in-stent stenosis rates.

INTRODUCTION: Our purpose was to analyze the long-term evolution of wide neck cerebral aneurysms treated with stent assistance. METHODS: Data of consecutive patients treated with the Neuroform stent over 9 years were retrospectively analyzed with emphasis on periprocedural complications, aneurysm occlusion grade evolution, and in-stent stenosis rates. RESULTS: Altogether, 113 patients with 117 unruptured and ruptured aneurysms were subject of analysis. Mean aneurysm size was 9.4 mm, and mean neck size was 4.7 mm. Procedural thromboembolic and hemorrhagic complications affected eight (6.8%) and four cases (3.4%), respectively. Immediate complete occlusion and occlusion with residual neck was achieved in 85% of cases, which at the first follow-up of 6 months, changed to 77 and 76 % at 36 months. Aneurysms ≥10 mm showed a higher tendency of recurrence. During the overall follow-up time ranging from 1 to 9 years, an in-stent stenosis of ≥50 % was observed only in three cases, all of them being asymptomatic. CONCLUSIONS: Stent-assisted coiling of wide neck aneurysms provided stable occlusion over the long-term follow-up, with very low and silent in-stent stenosis rates. Some incompletely occluded aneurysms showed a tendency of progressive occlusion; however, this was counterbalanced by the regrowth of others.

Posterior reversible encephalopathy syndrome (PRES): electroencephalographic findings and seizure patterns.

To better describe seizure type, frequency, and electroencephalographic (EEG) findings in posterior reversible encephalopathy syndrome (PRES) and correlate these data with clinical and magnetic resonance imaging (MRI) data, we retrospectively assessed medical charts and EEG studies of patients with PRES treated between 2004 and 2011. Data collected included patients' underlying pathology, lesion distribution by MRI, seizure type and frequency, EEG pathologic background activity, focal pathology, and epileptogenic activity. Thirty-eight of 49 adults with PRES suffered from seizures; 17 underwent EEG and were included in the analysis. Perpetuating factors were similar to those reported in the literature. In 15 of 17 patients, MRI showed widespread involvement rather than purely occipital lesions. Nine patients had subcortical and cortical involvement. Seizures were single short grand mal (GM) in 11, serial GM in 2, recurrent GM in 2, and additional focal seizures in 2. No seizures were noted beyond the first day. After discontinuation of antiepileptic medication, no patients experienced seizure recurrence during 6-month follow-up. EEG showed diffuse theta/delta slowing in 13 patients and epileptogenic activity with focal sharp-wave and periodic lateralizing epileptiform discharges in 2 patients. Seizures in PRES are most commonly single GM and are usually of limited duration. EEG shows variable theta/delta slowing. Focal EEG pathology is seen in patients with focal seizures. Seizures occur early after disease onset and terminate spontaneously or under therapy during the first 24 h. Seizure recurrence beyond 24 h and chronic epilepsy were not seen. Seizures in PRES are frequent but appear to be uncomplicated and do not herald worse prognosis. EEG is helpful in evaluating the degree of encephalopathy and monitoring epileptic activity. Long-term antiepileptic medication does not appear to be warranted.

Short term effects of magnetic resonance imaging on excitability of the motor cortex at 1.5T and 7T.

RATIONALE AND OBJECTIVES: The increasing spread of high-field and ultra-high-field magnetic resonance imaging (MRI) scanners has encouraged new discussion of the safety aspects of MRI. Few studies have been published on possible cognitive effects of MRI examinations. The aim of this study was to examine whether changes are measurable after MRI examinations at 1.5 and 7 T by means of transcranial magnetic stimulation (TMS). MATERIALS AND METHODS: TMS was performed in 12 healthy, right-handed male volunteers. First the individual motor threshold was specified, and then the cortical silent period (SP) was measured. Subsequently, the volunteers were exposed to the 1.5-T MRI scanner for 63 minutes using standard sequences. The MRI examination was immediately followed by another TMS session. Fifteen minutes later, TMS was repeated. Four weeks later, the complete setting was repeated using a 7-T scanner. Control conditions included lying in the 1.5-T scanner for 63 minutes without scanning and lying in a separate room for 63 minutes. TMS was performed in the same way in each case. For statistical analysis, Wilcoxon's rank test was performed. RESULTS: Immediately after MRI exposure, the SP was highly significantly prolonged in all 12 subjects at 1.5 and 7 T. The motor threshold was significantly increased. Fifteen minutes after the examination, the measured value tended toward normal again. Control conditions revealed no significant differences. CONCLUSION: MRI examinations lead to a transient and highly significant alteration in cortical excitability. This effect does not seem to depend on the strength of the static magnetic field.

Neuroimaging of infections of the central nervous system.

Neuroimaging plays a crucial role in the diagnosis and therapeutic management of neurologic infections. This article summarizes imaging findings in brain abscesses, ventriculitis, viral diseases, and opportunistic infections. In cases of uncomplicated meningitis, cranial computed tomography is sufficient to exclude brain edema, hydrocephalus, and skull base pathology. Magnetic resonance imaging (MRI) is superior in depicting complications (e.g., empyema, vasculitis). Diffusion-weighted imaging (DWI) shows parenchymal complications of meningitis earlier and is of help in differentiation of pyogenic abscess from other ring-enhancing lesions. Proton magnetic resonance spectroscopy can produce specific peak-patterns in cases of abscess, such as the presence of lactate and cytosolic amino acids. In toxoplasmosis, DWI may help to differentiate from lymphoma, showing no restriction of water diffusion. In patients with viral encephalitis, DWI allows earlier lesion detection. MRI has revolutionized the rapid diagnosis of spinal abscess.

Transcranial sonography of the third ventricle and cognitive dysfunction in HIV patients.

BACKGROUND: Although the incidence and prevalence of dementia associated with human immunodeficiency virus (HIV) infection has decreased since the introduction of highly active antiretroviral therapy, cognitive dysfunction remains one of the most prevalent factors severely affecting quality of life in patients with HIV. Previous magnetic resonance imaging (MRI) studies showed a correlation between brain atrophy, enlargement of the ventricles and cognitive impairment in HIV patients. OBJECTIVE: To investigate the usefulness of transcranial sonographic (TCS) measurement of the third ventricle in detection of brain atrophy in HIV patients and the correlation with neuropsychological deficits. METHODS: We examined 47 HIV patients and 40 healthy age-matched controls with TCS, neuroimaging (cranial MRI or computed tomography) and a neuropsychological test battery. RESULTS: The third ventricle was significantly larger in patients than in healthy controls and correlated significantly with duration of HIV, Center of Disease Control (CDC) stage, CD4 lymphocytes and distinct cognitive and motor deficits. CONCLUSION: TCS cannot replace neuroimaging but is a valuable method in the detection of brain atrophy and follow-up of HIV patients at risk or with a recent diagnosis of HIV encephalopathy.

Carotid intima-media thickness in HIV-infected individuals: relationship of premature atherosclerosis to neuropsychological deficits?

BACKGROUND: Intima-media thickness (IMT) measured by extracranial duplex sonography is a surrogate marker for atherosclerosis. It is well known that IMT is greater in HIV patients than in age-matched healthy controls due to HIV- induced endothelial damage and metabolic side-effects of antiretroviral therapy. However, it remains unclear whether atherosclerosis has an additional impact on cognitive function in HIV patients. Therefore, the objective of this study was to investigate the correlation between IMT and neuropsychological deficits in HIV patients. METHODS: 47 HIV patients and 40 age-matched healthy controls were examined by extracranial ultrasound 2 and 3 cm before the flow divider to evaluate differences in IMT. Possible neuropsychological deficits in HIV patients were assessed using a battery of 10 neuropsychological tests. Results of neuropsychological tests and markers of disease severity were correlated with IMT in HIV patients. RESULTS: IMT was significantly greater in patients than in healthy controls (p < 0.001). However, none of the neuropsychological tests correlated significantly with IMT measurements in HIV patients. There was only a weak correlation between deficits in attention and IMT in HIV patients (r = 0.44; p = 0.005), which was non-significant after correction for multiple comparisons. Markers of disease severity (CD4 cell count, HIV load in plasma, duration of HIV disease) did not correlate with IMT either. CONCLUSION: IMT was greater in HIV patients compared to age-matched controls but it appears that premature atherosclerosis has no additional impact on the evolution of neuropsychological deficits in HIV patients. IMT did not correlate with the severity of immunodeficiency.

Visual cortex excitability in migraine evaluated by single and paired magnetic stimuli.

OBJECTIVE: To determine the excitability of the visual cortex by phosphene thresholds (PT) in patients with migraine using transcranial magnetic stimulation (TMS) with single- and paired-pulses. METHODS: Nineteen patients with migraine with aura (MWA), 19 patients with migraine without aura (MWoA), and 22 control subjects were included. Patients were free from preventive anti-migraine treatment and were investigated within 3 days before or after an acute migraine attack. In each subject, PT were assessed by single-pulse and paired-pulse TMS with an interstimulus interval of 50 ms. RESULTS: The main effect of diagnosis indicated that mean PT were significantly lower in migraine patients than in control subjects (P = .001). Using single-pulse TMS, mean PT tended to be lower in MWoA-patients (57.7 +/- 11.8%) compared with control subjects (64.4 +/- 10.5%) (P = .064). In MWA-patients, mean PT (53.1 +/- 5.7%) were significantly lower compared with controls (P < .001). Using TMS with paired pulses, mean PT were significantly reduced in MWoA-patients (40.3 +/- 4.9%, P = .017) as well as in MWA-patients (39.6 +/- 4.2%, P = .005) compared with controls (44.6 +/- 6.0%). The main effect of stimulation type indicated that mean PT were lower determined with paired-pulse stimulation than with single pulses (P < .001). CONCLUSIONS: PT are reduced in patients with migraine in the interictal state suggesting an increased excitability of visual cortical areas. Compared with single-pulse TMS, paired-pulse magnetic stimulation is more efficient to elicit phosphenes. This technique provides the opportunity to evaluate visual cortex excitability with lower stimulus intensities and less discomfort.

Neuroimaging of infections.

Neuroimaging plays a crucial role in the diagnosis and therapeutic decision making in infectious diseases of the nervous system. The review summarizes imaging findings and recent advances in the diagnosis of pyogenic brain abscess, ventriculitis, viral disease including exotic and emergent viruses, and opportunistic disease. For each condition, the ensuing therapeutic steps are presented. In cases of uncomplicated meningitis, cranial computed tomography (CT) appears to be sufficient for clinical management to exclude acute brain edema, hydrocephalus, and pathology of the base of skull. Magnetic resonance imaging (MRI) is superior in depicting complications like sub-/epidural empyema and vasculitic complications notably on FLAIR (fluid-attenuated inversion recovery)-weighted images. The newer technique of diffusion-weighted imaging (DWI) shows early parenchymal complications of meningitis earlier and with more clarity and is of help in differentiation of pyogenic abscess (PA) from ring enhancing lesions of other etiology. Proton magnetic resonance spectroscopy (PMRS) seems to produce specific peak patterns in cases of abscess. The presence of lactate cytosolic amino acids and absence of choline seems to indicate PA. Also in cases of suspected opportunistic infection due to toxoplasma DWI may be of help in the differentiation from lymphoma, showing no restriction of water diffusion. In patients with herpes simplex and more exotic viruses like West Nile and Murray Valley virus DWI allows earlier lesion detection and therapeutic intervention with virustatic drugs.