High resolution sonography in the evaluation of the peripheral nervous system in polyneuropathy--a review of the literature.

Clinical, laboratory and electrodiagnostic studies are the mainstay in the diagnosis of polyneuropathy. An accurate etiological diagnosis is of paramount importance to provide the appropriate treatment, prognosis and genetic counselling. High resolution sonography of the peripheral nervous system allows nerves to be readily visualized and to assess their morphology. Ultrasonography has brought pathophysiological insights and substantially added to diagnostic accuracy and treatment decisions amongst mononeuropathies. In this study the literature on its clinical application in polyneuropathy is reviewed. Several polyneuropathies have been studied by means of ultrasound: Charcot-Marie-Tooth, hereditary neuropathy with liability to pressure palsies, chronic inflammatory demyelinating polyneuropathy, Guillain-Barré syndrome, multifocal motor neuropathy, paraneoplastic polyneuropathy, leprosy and diabetic neuropathy. The most prominent reported pathological changes were nerve enlargement, increased hypo-echogenicity and increased intraneural vascularization. Sonography revealed intriguingly different patterns of nerve enlargement between inflammatory neuropathies and axonal and inherited polyneuropathies. However, many studies concerned case reports or case series and showed methodological shortcomings. Further prospective studies with standardized protocols for nerve sonography and clinical and electrodiagnostic testing are needed to determine the role of nerve sonography in inherited and acquired polyneuropathies.

[Glossopharyngeal nerve neuralgia: not just a sore throat]. / Nervus glossopharyngeus-neuralgie: niet alleen pijn in de keel.

In this article we describe six cases of glossopharyngeal neuralgia. The characteristic attacks of lancinating pain in throat, ear and tongue can be accompanied by symptoms such as coughing, hoarseness, stridor and fainting. These symptoms can also occur without the pain, which may lead to frequent misdiagnosis and unnecessary investigations. The drugs of choice are carbamazepine, phenytoin and lithium. Persisting symptoms may require an operation.

Multifocal enlargement and increased vascularization of peripheral nerves detected by sonography in CIDP: a pilot study.

OBJECTIVE: Detection of nerve enlargement in polyneuropathies by sonography is a new research area. No systematic investigation has been done yet in chronic inflammatory demyelinating polyneuropathy (CIDP). Therefore we investigated this in CIDP. METHODS: Eleven patients with CIDP fulfilling the international criteria on CIDP underwent ultrasonographic examination of the median, ulnar, fibular and posterior tibial nerves and sometimes the brachial plexus bilaterally, using a standardized protocol. We assessed presence of nerve thickening and increased nerve vascularization. RESULTS: In 7 of the 11 patients multiple nerve enlargements were detected: ulnar nerve 7, fibular nerve 5, posterior tibial nerve 4 and median nerve in 4 patients. The number of enlarged nerves was related with the MRC sum-score (p=0.03) and the total protein in the cerebrospinal fluid (CSF) at diagnosis (p=0.02). Increased vascularization was seen in 6 of the 11 patients: 4 in one nerve and in 2 in multiple nerves. The number of nerves with increased vascularization was associated with the number of enlarged nerves (p=0.01) and total protein in the CSF (p=0.006). CONCLUSION: Multiple nerve enlargements occur in CIDP showing a relation with a lower MRC sum-score, increased nerve vascularization and a higher total protein of the CSF. SIGNIFICANCE: Our findings of nerve enlargement and increased nerve vascularization may be tools to monitor disease activity in CIDP, but further studies are needed.

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.

High-performance liquid chromatographic determination of carbamazepine and metabolites in human hair.

To study the use of hair analysis in monitoring drug compliance and historical changes in pharmacokinetics we developed a method for the quantitative determination of the anti-epileptic drug carbamazepine (CBZ) and trans-10,11-dihydro-10,11-dihydroxy-carbamazepine (CBZ-diol) in hair from carbamazepine users. Digestion by 1 M NaOH was found to be the best method for isolating CBZ and CBZ-diol from hair, followed by solid-phase extraction and reversed-phase HPLC with UV detection. Recoveries from spiked hair samples were 76-86%. Within-day precision (C.V.; n = 10) for CBZ and CBZ-diol in hair of a CBZ user containing 10.9 microg/g CBZ and 3.2 microg/g CBZ-diol were 1.7 and 5.0%, respectively. Sectional hair analysis of a patient on a constant dosage of CBZ demonstrates an exponential decrease in hair concentrations of CBZ and CBZ-diol with increasing distance from the root, probably caused by shampooing. No CBZ-10,11-epoxide (CBZ-epox) could be detected. However, one component in the chromatogram is probably CBZ-beta-hydroxythioether, an adduct of CBZ-epox with cysteine, or acridinethioacetal, its rearrangement product. The concentration of this component does not decrease with increasing distance from the root.

Is 11C-flumazenil PET superior to 18FDG PET and 123I-iomazenil SPECT in presurgical evaluation of temporal lobe epilepsy?

OBJECTIVE: To determine the contribution of 18FDG PET, 11C-flumazenil PET, and 123I-iomazenil SPECT to the presurgical evaluation of patients with medically intractable complex partial seizures. METHODS: Presurgical evaluation was performed in 23 patients, who were considered candidates for temporal lobe resective surgery (14 females and nine males with a median age of 34 (range 13 to 50) years). The presurgical diagnosis was based on seizure semiology as demonstrated with ictal video recording, ictal and interictal scalp EEG recordings, and MRI. RESULTS: Eighteen patients had convergent findings in clinical semiology, interictal and ictal EEG with scalp and sphenoidal electrodes, and MRI that warranted surgery without depth EEG (DEEG). In five patients with insufficient precision of localisation, DEEG with intracerebral and subdural electrodes was performed. MRI showed abnormalities in 22 out of 23 patients. Of these 22, 18 had mesial temporal sclerosis. This was limited to the mesial temporal lobe in four and more widespread in the temporal lobe in 14 patients. In one patient only enlargement of the temporal horn was found and in three others only white matter lesions were detected. 18FDG PET showed a large area of glucose hypometabolism in the epileptogenic temporal lobe, with an extension outside the temporal lobe in 10 of 23 patients. Only in one of these patients DEEG showed extratemporal abnormalities that were concordant with a significant extratemporal extension of hypometabolism in 18FDG PET. 18FDG PET was compared with the results of scalp EEG: in none of the patients was an anterior temporal ictal onset in scalp EEG related to a maximum hypometabolism in the mesial temporal area. By contrast, the region of abnormality indicated by 11C-flumazenil PET was much more restricted, also when compared with DEEG findings. Extension of abnormality outside the lobe of surgery was seen in only two patients with 11C-flumazenil and was less pronounced compared with the intratemporal abnormality. Both 18FDG PET and 11C-flumazenil PET reliably indicated the epileptogenic temporal lobe. Thus these techniques provide valuable support for the presurgical diagnosis, especially in patients with non-lesional MRI or non-lateralising or localising scalp EEG recordings. In those patients in whom phase 1 presurgical evaluation on the basis of classic methods does not allow a localisation of the epileptogenic area, PET studies may provide valuable information for the strategy of the implantation of intracranial electrodes for DEEG. Previous studies have suggested that 11C-flumazenil binding has a closer spatial relationship with the zone of ictal onset than the area of glucose hypometabolism, but this study suggests rather that the decrease in the 11C-flumazenil binding simply reflects a loss of neurons expressing the benzodiazepine-GABA receptor. 11C-flumazenil PET did not prove to be superior to 18FDG PET. CONCLUSION: In 21 patients sufficient material was obtained at surgery for a pathological examination. In 17 mesial temporal sclerosis, in one an oligodendroglioma grade B, in another a vascular malformation and in two patients no abnormalities were found. Although all 21 patients with pathological abnormality showed hypometabolic zones with 18FDG PET and a decreased uptake in 11C-flumazenil binding, there was no strong correlation between pathological diagnosis and functional abnormal areas in PET. Grading of medial temporal sclerosis according to the Wyler criteria showed no correlation with the degree of hypometabolism in either 18FDG or 11C-flumazenil PET. The interictal 123I-iomazenil SPECT technique was highly inaccurate in localising the lobe of surgery.

Intracranial EEG seizure-offset termination patterns: relation to outcome of epilepsy surgery in temporal lobe epilepsy.

PURPOSE: Studies using stereo-EEG (SEEG) and electrocorticography (ECoG) should not only identify a patient's epileptogenic zone, but also should provide prognostic information for surgical outcome. In this respect, seizure-offset patterns have so far been the subject of only one study, in which they were shown to be associated with poor outcome when recorded over cortical areas outside the temporal lobe of seizure onset. To clarify whether seizure-offset patterns are reliable in predicting seizure outcome, we studied SEEG/ECoG in a similar group of patients with temporal lobe epilepsy (TLE). METHODS: SEEG/ECoG records of 44 patients with refractory TLE were analyzed. The areas of seizure termination were classified as ipsilateral or contralateral (mesial and/or lateral) temporal, (temporal and) frontal, and diffuse/bilateral. Patients were classified with respect to seizure outcome as either seizure-free (UCLA class 1a) or not seizure free (UCLA class 2-4); both groups were correlated with specific seizure-offset categories using Fisher's exact probability test and analysis of variance (ANOVA). RESULTS: Of the 44 patients, the majority (n = 36) had at least part of their seizure offsets in the ipsilateral temporal lobe, whereas 8 patients manifested no seizure offsets in this lobe. Only 9 patients (20%) showed exclusive offsets in the ipsilateral temporal lobe. No statistically significant difference was evident between patients with all seizure offsets in the ipsilateral temporal lobe and those with offsets elsewhere. Similarly, no statistically significant difference was evident between patients with a diffuse seizure offset and those with seizure offsets of a different category. CONCLUSIONS: Seizure-offset patterns in SEEG/ECoG are unreliable in predicting seizure outcome after resective activity surgery for TLE.

Comparison of combined versus subdural or intracerebral electrodes alone in presurgical focus localization.

PURPOSE: The yield of subdural versus intracerebral electrodes for ictal localization remains a point of controversy. We assessed the relative sensitivity of these two types of electrodes per case. METHODS: Eighty-three intracranial recordings obtained from 82 patients were retrospectively reviewed to establish which type of electrode performed best in which patients and which seizure types. RESULTS: Sixty (73%) of 82 patients had temporal lobe seizure onsets, eight frontal, nine widespread or multifocal/multilobar or both, whereas in five, seizure onset was not localized. Exclusive use of intracerebral electrodes would have been sufficient for accurate localization of the seizure-onset zone in all 35 patients with strictly mesial temporal seizure onsets. In only 20 (57%) of these 35 patients, the same decision would have been reached with exclusive use of subdural electrodes. In widespread neocortical and mesial temporal seizures (n = 25), yield of both electrode types was at about the same level, but neither was sufficient to identify the zone of ictal onset on its own. In frontal or multilobar seizures (n = 22), yield of subdural electrodes was slightly better then that of the intracerebral electrodes, but was not sufficient in all cases. CONCLUSIONS: This study indicates that, depending on the characteristics of the seizure disorder, exclusive use of either intracerebral or subdural electrodes may easily result in erroneous diagnosis because of insufficient sampling of the brain. These findings are in contrast with other studies emphasizing the high yield of reliable EEG findings in evaluations with a single type of electrode and corroborate the results of one of our previous studies.

Pharmacokinetics and pharmacodynamics of midazolam administered as a concentrated intranasal spray. A study in healthy volunteers.

AIMS: To investigate the pharmacokinetic and pharmacodynamic profile of midazolam administered as a concentrated intranasal spray, compared with intravenous midazolam, in healthy adult subjects. METHODS: Subjects were administered single doses of 5 mg midazolam intranasally and intravenously in a cross-over design with washout period of 1 week. The total plasma concentrations of midazolam and the metabolite 1-hydroxymidazolam after both intranasal and intravenous administration were described with a single pharmacokinetic model. beta-band EEG activity was recorded and related to midazolam plasma concentrations using an exponential pharmacokinetic/pharmacodynamic model. RESULTS: Administration of the intranasal spray led to some degree of temporary irritation in all six subjects, who nevertheless found intranasal administration acceptable and not painful. The mean (+/-s.d.) peak plasma concentration of midazolam of 71 (+/-25 ng ml-1) was reached after 14 (+/-5 min). Mean bioavailability following intranasal administration was 0.83+/-0.19. After intravenous and intranasal administration, the pharmacokinetic estimates of midazolam were: mean volume of distribution at steady state 1.11+/-0.25 l kg-1, mean systemic clearance 16.1+/-4.1 ml min-1 kg-1 and harmonic mean initial and terminal half lives 8.4+/-2.4 and 79+/-30 min, respectively. Formation of the 1-hydroxymetabolite after intranasal administration did not exceed that after intravenous administration. CONCLUSIONS: In this study in healthy volunteers a concentrated midazolam nasal spray was easily administered and well tolerated. No serious complications of the mode of administration or the drug itself were reported. Rapid uptake and high bioavailability were demonstrated. The potential of midazolam given via a nasal spray in the acute treatment of status epilepticus and other seizure disruptions should be evaluated.