Franz Xaver Glocker

Pain perception during self-reported distress and calmness in patients with borderline personality disorder and self-mutilating behavior

Self-mutilation occurs in 70-80% of patients who meet DSM-IV criteria for borderline personality disorder. Approximately 60% of these patients report that they do not feel pain during acts of self-mutilation such as cutting or burning. Findings of recent studies measuring pain perception in patients with BPD are difficult to interpret since variables such as distress, dissociation or relevant psychotropic medication have not been controlled. The Cold Pressor Test (CPT) and the Tourniquet Pain Test (TPT) were administered to 12 female patients with BPD who reported analgesia during self-mutilation and 19 age-matched healthy female control subjects. All subjects were free of psychotropic medication. The patients were studied on two occasions: during self-reported calmness and during intensive distress (strong urge to cut or burn themselves). Even during self-reported calmness, patients with BPD showed a significantly reduced perception of pain compared to healthy control subjects in both tests. During distress, pain perception in BPD patients was further significantly reduced as compared with self-reported calmness. The present findings show that self-mutilating patients with BPD who experience analgesia during self-injury show an increased threshold for pain perception even in the absence of distress. This may reflect a state-independent increased pain threshold which is further elevated during stress. Interpretation of these findings is limited by their reliance upon self-reports.

Central mechanisms in human enhanced physiological tremor

The sites of the central nervous structures involved in enhanced physiological tremor (EPT) are still unclear. The syndrome of persistent mirror movements (PMM) is characterized by abnormal bilateral corticospinal projections. If a supraspinal mechanism is involved in EPT, the activity of EPT should be coherent between both sides in subjects with this abnormality. We investigated three PMM subjects and three normal controls. Focal transcranial magnetic stimulation (TMS) resulted in contralateral hand muscle responses in the controls. The PMM subjects, in contrast, had bilateral responses. Similarly, long-latency reflexes (LLR) in PMM could be recorded bilaterally, while the control subjects showed responses only on the stimulated side. EPT was evoked by intravenous salbutamol. EMG time series were recorded bilaterally from the wrist extensor muscles and cross spectra were calculated. If there was a significant right-left-coherence, phase analysis was performed. No control subject showed a significant right-left-coherence of tremor activity. In contrast, a significant coherence was found in PMM between 8 and 12 Hz. When the mechanical tremor frequency of one hand was reduced by loading, coherences and phase spectra of the EMGs remained unchanged. By comparing the results from TMS, LLR and cross spectral analysis we come to the conclusion, that the 8 to 12 Hz component of EPT is transmitted transcortically, most likely originating from two separate generators for both sides.

Electrophysiological characteristics of lesions in facial palsies of different etiologies. A study using electrical and magnetic stimulation techniques.

Using magnetic stimulation techniques in addition to conventional electrical stimulation, the entire facial motor pathway can be assessed electrophysiologically. To study the diagnostic yield of these examinations, 174 patients with facial palsies of a variety of etiologies were examined (85 Bells palsies, 24 Guillain-Barré syndrome (GBS), 19 Lyme borreliosis, 17 zoster oticus, 12 meningeal affections, 10 brain-stem disorders and 7 HIV-related facial palsies). The facial nerve was stimulated electrically at the stylomastoid fossa and magnetically within its canalicular portion. Additionally, the face-associated contralateral motor cortex was stimulated magnetically. Recordings were from the nasalis or mentalis muscle, or both, using surface electrodes. Bells palsy patients showed typically a unilateral local hypoexcitability of the facial nerve to canalicular stimulation. In GBS, bilateral latency prolongations were frequent, as expected for a myelinic disorder. In contrast, in zoster, predominant axonotmesis was unilateral, and in HIV infection sometimes bilateral. The method was very sensitive to detect subclinical dysfunctions in meningo-radiculitis and malignant meningeal diseases, either prior to the onset of palsy, or on the contralateral (clinically unaffected) side. It also distinguished reliably between central and peripheral facial motor pathway lesions. In our experience, these inexpensive and non-invasive electrophysiological techniques contribute substantially to the differential diagnosis of facial palsies.

Modulation of upper extremity motor evoked potentials by cutaneous afferents in humans

The excitability of motoneurons controlling upper limb muscles in humans may vary with cutaneous nerve stimulation. We investigated the effect of noxious and non-noxious conditioning stimuli applied to right and left digit II and right digit V on motor evoked potentials (MEPs) recorded from right thenar eminence, abductor digiti minimi, biceps and triceps brachii muscles in twelve healthy subjects. Transcranial magnetic stimulation (TMS) was applied at interstimulus intervals (ISI) ranging from 40 to 160 ms following conditioning distal digital stimulation. TMS and transcranial electrical stimulation (TES) were compared at ISI 80 ms. Painful digital stimulation caused differential MEP amplitude modulation with an early maximum inhibition in hand muscles and triceps brachii followed by a maximum facilitation in arm muscles. Stimulation of different digits elicited a similar pattern of MEP modulation, which largely paralleled the behavior of cutaneous silent periods in the same muscles. Contralateral digital stimulation was less effective. MEPs following TMS and TES did not differ in their response to noxious digital stimulation. MEP latencies were shortened by cutaneous stimuli. The observed effects were stimulus intensity dependent. We conclude that activation of A-alpha and A-delta fibers gives rise to complex modulatory effects on upper limb motoneuron pools. A-delta fibers initiate a spinal reflex resulting in MEP amplitude reduction in muscles involved in reaching and grasping, and MEP amplitude facilitation in muscles involved in withdrawal. These findings suggest a protective reflex mediated by A-delta fibers that protects the hand from harm. A-alpha fibers induce MEP latency shortening possibly via a transcortical excitatory loop.

Modulation of upper extremity motoneurone excitability following noxious finger tip stimulation in man: a study with transcranial magnetic stimulation

Little is known about nociceptive reflex mechanisms in the upper limb in humans. To investigate nociceptive effects on spinal motoneurone excitability, a conditioning noxious stimulus was applied to the index finger of five healthy subjects. Motor evoked potentials (MEPs) following contralateral transcranial magnetic stimulation (TMS) were recorded from thenar eminence (TE) and biceps brachii (BB) muscles ipsilateral to finger stimulation. TMS was randomly applied alone or combined with preceding finger stimulation at an interstimulus interval of 100 ms. MEP amplitudes were profoundly suppressed in TE and augmented in BB. We conclude that nociception produces a differential effect on different spinal motoneurone pools, which may be part of a complex protective reflex mechanism in the upper limb of humans.

Magnetic transcranial and electrical stylomastoidal stimulation of the facial motor pathways in Bell's palsy: time course and relevance of electrophysiological parameters

Facial nerve motor neurography was performed at various times after the onset of Bells palsy in 97 patients. Stimulation of the facial nerve was performed (1) electrically in the fossa stylomastoidea (ElStim), and (2) magnetically in the labryinthine segment of the facial canal (MagStim), evaluating different coil positions over the skull. Additionally, the face-associated motor cortex was stimulated magnetically in 47 patients (CxStim). A marked reduction of the amplitudes of the compound muscle action potentials (CMAP) evoked by MagStim on either m. nasalis or mentalis, or both, was observed which was clearly more pronounced than the amplitude reduction to ElStim. This discrepancy occurred very early during the disease, the mean amplitude (expressed in percent of the amplitude on the unaffected side) being 82% (S.D. 9.1) for ElStim and 1% (2.7) for MagStim at days 0-4. It persisted for several months, often when facial nerve function had recovered to normal, as assessed by clinical observation, ElStim, and CxStim. This amplitude decrease to MagStim, which appears to be related to a locally enhanced stimulation threshold of the facial nerve, is a very sensitive and reproducible finding in Bells palsy. It may prove specific of the disorder, of diagnostic value, and of interest in the follow-up of patients during treatment trials.

Valproic acid triggers acute rhabdomyolysis in a patient with carnitine palmitoyltransferase type II deficiency

A 47-year-old man suffering from a bipolar disorder and intermittent myoglobinuria presented with acute rhabdomyolysis with renal failure after starting therapy with valproic acid. On morphological examination, skeletal muscle revealed increased lipid storage. Biochemically, decreased enzyme activity of carnitine palmitoyltransferase (CPT) type II with carnitine levels in the lower limit was found. Genetic analysis detected the common Ser113Leu substitution on one allele of the CPT2 gene. We conclude that valproic acid should be avoided in patients with CPT type II deficiency.

Maturation of inhibitory and excitatory motor cortex pathways in children

OBJECTIVE To study intracortical inhibition and facilitation with paired-pulse transcranial magnetic stimulation in children, adolescents and adults. METHODS Paired-pulse transcranial magnetic stimulation (interstimulus intervals (ISI): 1, 3, 5, 10 and 20 ms) was applied over the primary motor cortex (M1) in 30 healthy subjects (range 6-30 years, median age 15 years and 8 months, SD 7,9) divided in three groups: adults (>or=18 years), adolescents (> 10 and < 18 years) and children (<or=10 years). RESULTS We observed significantly less intracortical inhibition (SICI) in childrens M1 compared to that of adults. Adolescents showed significantly less SICI at the 5 ms interval than did adults. No significant differences were apparent in intracortical facilitation (ICF). CONCLUSION We postulate that, as in adults, the maturing M1 possesses horizontal glutamatergic cross-links that represent the neuronal substrate of excitatory intracortical pathways. GABAergic interneurons, the neuronal substrate of inhibitory intracortical pathways, mature between childhood and adulthood. Reduced GABAergic inhibition may facilitate neuronal plasticity and motor learning in children.

Effects of local injections of botulinum toxin on electrophysiological parameters in patients with hemifacial spasm: role of synaptic activity and size of motor units

Ten patients with typical hemifacial spasm were examined before and after treatment with local injections of botulinum toxin type A. After a mean follow-up period of 38 days there was a reduction of the compound muscle action potential (CMAP) of the injected orbicularis oculi muscle of 40%. Ephaptic transmission studied by selective stimulation of facial nerve branches revealed a preserved delayed response of the affected mentalis muscle. However, no delayed response could be recorded in the injected orbicularis oculi muscle in nine patients. The discrepancy between complete loss of the delayed (ephaptic) response and only moderate reduction of the CMAP amplitude of the direct response may be explained by preferential uptake of botulinum toxin type A by hyperactive synapses involved in ephaptic transmission.

Treatment of neuropathic bladder using botulinum toxin A in a 1-year-old child with myelomeningocele

Sirs, Intramuscular injection of botulinum toxin A (BTX/A) is an effective and safe therapy for children and adults with dystonic and spastic movement disorders [1, 2]. Furthermore, clinical trials have been successfully carried out treating neuropathic bladder under various conditions [3, 4, 5, 6]. We report the successful treatment with BTX/A of a neuropathic bladder in a 1-year-old boy with myelomeningocele (MMC), which has not, to our knowledge, been described in the literature before. The 1-year-old male patient showed MMC extending from Th9 to L1. Consolidation of the large wound on his back was complicated by recurrent infections. The child had an Arnold-Chiari malformation with severe hydrocephalus and showed no active lower limb movements. However, there was severe muscular hypertonus of the rectus femoris muscle and the adductor muscles. Rectal palpation suggested a highly active sphincter ani externus muscle, causing severe constipation. Starting at the age of 9 months, the child suffered from recurrent urinary tract infections with multi-resistant Pseudomonas, at a frequency of up to twice a month, although he had been circumcised. Over a period of 12 weeks, repeated sonographic evaluation of the urinary tract revealed post-void residual urine volumes of 75, 100, 150, and 80 ml. Each measurement was performed three times post voiding and the lowest value was taken. Neither reflux nor hydronephrosis was observed. Intermittent catheterization was carried out, but was not accepted as a first-line treatment by the parents. Extensive urodynamic studies were not undertaken because a prolonged supine position was strictly prohibited due to the wound on his back. In order to evaluate the external urethral sphincter, we performed a needle electromyogram (EMG), which revealed an overactive muscle. Treatment with BTX/A was carried out after obtaining approval from the local ethics committee and informed consent from the parents. The external urethral sphincter was treated with 40 units BTX/A (Botox, Merz, Frankfurt, Germany, 100 units diluted in 2 ml), by transperineal injection using EMG guidance. Two injection points were used. The child was sedated with midazolam. Thereafter, we performed a sonographic evaluation of post-void residual urine volume at weekly intervals. The volume before treatment with BTX/A was about 80 ml; during the 3 weeks after treatment, it decreased to below 5 ml (Fig. 1).