Martin Winterholler

Iatrogenic (para-) spinal abscesses and meningitis following injection therapy for low back pain.

&NA; Low back pain is often treated with paraspinal injections of analgesics and steroids. Infectious complications of these techniques are rare but they can potentially hold high risks for the patients. History and clinical data of all patients admitted to a neurological unit suffering from community acquired purulent meningitis were prospectively analyzed during an 8 year interval (1992 and 2000) with special regard to the previous medical history. One hundred and twenty eight patients were included in the study. Eight out of 128 patients (6.25%) had a history of single or repeated paravertebral (4/8), facet‐joint (2/8), peridural (1/8) or spinal (1/8) injections 2–21 days before admission to the hospital. In six out of eight patients either Staphylococcus aureus (4/8) or coagulase‐negative staphylococci (2/8) were found in the cerebro spinal fluid (CSF), in two patients no causative organism was detected. One patient died, three survived with sequel. Repeated paraspinal, peridural or spinal injections with analgesic drugs in combination with corticosteroids hold a risk for parameningeal inoculation of bacteria resulting in paraspinal, spinal, and epidural abscesses or meningitis. The absolute frequency of these complications may be rare but they are responsible for a considerable proportion of community acquired purulent CNS infections.

Botulinum neurotoxin type A injections reduce spasticity in mild to moderate hereditary spastic paraplegia— Report of 19 cases

Hereditary spastic paraplegia (HSP) is characterized by lower extremity spasticity. Symptomatic therapy generally includes physical therapy and oral antispastic agents, in selected cases intrathecal baclofen. Because of the positive results in other treatments of spasticity, the use of botulinum neurotoxin type A (BoNT‐A) might also be considered for patients with HSP. We report the effect of BoNT‐A injections in 19 unselected patients with HSP treated by the members of the German Spasticity Education Group. In 17 patients, the modified Ashworth scale had improved by one point. In one patient, it improved by three points. Most of the patients reported reduction of spasticity. BoNT‐A injections were continued in 11 of 19 patients (57.9%). All of the patients with continued injections had a good or very good global subjective improvement. Patients with less pronounced spasticity and patients with accompanying physical therapy tended to exhibit a better effect. Only four patients reported adverse effects which were increased weakness in three patients and pain in one patient. BoNT‐A injections appear to reduce spasticity effectively and safely, especially in patients with mild to moderate spasticity. The preliminary results of our case series should encourage larger studies of BoNT‐A injections in HSP.

Botulinum toxin in patients with multiple sclerosis

Nearly all patients with multiple sclerosis (MS) will develop spasticity in the course of their disease. This symptom accounts for most of the handicap and impairment in the quality of life. Treatment with botulinum toxin will enable an efficient and safe alleviation of spasticity and the problems involved, given a realistic definition of the therapeutic target and a graded multimodal approach. Treatment may fail for a great number of reasons that require diligent analysis. Compared with other disorders resulting in spasticity as well, MS does not constitute a monophasic disorder but is influenced by many factors. Treatment of spasticity in MS must therefore be guided by its particular aspects.

Botulinum toxin A (Botox®) and sweating-dose efficacy and comparison to other BoNT preparations

BACKGROUND Botulinum toxin type A (BoNT/A) is 20-50 times more effective than Botulinum toxin type B (BoNT/B) concerning the treatment of muscular hypercontractions [Sloop, R.R., Cole, B.A., Escutin, R.O., 1997. Human response to botulinum toxin injection: type B compared with type A. Neurology 49, 189-194]. Botulinum toxins block motor nerves as well as autonomic fibres [Rand, M.J., Whaler, B.C., 1965. Impairment of sympathetic transmission by botulinum toxin. Nature 206, 588-591]. OBJECTIVE Purpose of this study was to analyse the dose dependent reduction of sweating using the BoNT/A preparation Botox and to compare the results with our earlier results analysing Dysport [Braune, C., Erbguth, F., Birklein, F., 2001. Dose thresholds and duration of the local anhidrotic effect of botulinum toxin injections: measured by sudometry. Br. J. Dermatol. 144, 111-117] and Neurobloc (BoNT/B) [Birklein, F., Eisenbarth, G., Erbguth, F., Winterholler, M., 2003. Botulinum toxin type B blocks sudomotor function effectively: a 6 month follow up. J. Invest. Dermatol. 121, 1312-1316]. METHODS Different doses of Botox were injected subcutaneously (n=27 healthy subjects). Planimetrical analyses of the area of anhidrosis and quantitative sudomotor-axon-reflex testing (QSART) were done after 3 weeks, 3 and 6 months. RESULTS A threshold dose of 1.25 MU Botox led to anhidrotic skin spots after 3 weeks. The duration of anhidrosis was prolonged for 3 months when 17.5 MU and for 6 months when 50 MU were injected. Anhidrotic area size decreased with time (p=0.001), indicating partial recovery at the edges. After 3 weeks, QSART had significantly decreased to 29% of baseline. With doses of 70 MU or more it decreased to zero. After 3 months, QSART had returned to 68% of baseline and after 6 months to 87%. CONCLUSIONS Botox dose-dependently suppressed sweating. Comparison to Dysport and Neurobloc revealed a strikingly similar efficacy after 3 weeks and 3 months for all preparations. BoNT/A in general induced a more sustained anhidrosis than BoNT/B.

Intravascular lymphomatosis mimicking disseminated encephalomyelitis and encephalomyelopathy

Intravascular lymphomatosis is characterized by the presence of large lymphoma cells predominantly within small vessels. This report presents two patients with diagnostically misleading neurological manifestation of this disease. Case 1, a 63-year-old man, developed a sensorimotor transverse spinal cord syndrome and encephalopathy. Lumbar puncture revealed albuminocytological dissociation. Magnetic resonance imaging (MRI) showed progression of multifocal infarct-like lesions in the brain, the thoracic cord and the medullary cone. Autoimmune inflammation was suspected, and the patient received immunosuppressive therapy with immunoglobulins, steroids and azathioprine. He died 18 months after the onset of symptoms. Case 2, a 68-year-old man, showed fluctuating aphasia, disorientation, and fever for several months. Brain MRI-scan, electroencephalography (EEG) and cerebrospinal fluid (CSF) cytology were inconclusive. Premortal biopsy of lesions in liver and right suprarenal gland showed no further characterized malignancy. He died 6 months after the first occurrence of symptoms. Autopsy of both cases revealed an intravascular lymphomatosis. Tumour cells were seen disseminated in extranodal sites including heart, lung, adrenal gland, spleen, thyroid gland and brain. An intravascular lymphomatosis should be considered when a meningoencephalitic symptomatology is unclear. A biopsy of different organs including the brain and leptomeninges should not be delayed to ensure ante mortem diagnosis and to initiate chemotherapy.

Sudomotor testing predicts the presence of neutralizing botulinum A toxin antibodies

The increasing number of patients being treated with botulinum toxin A complex (BoNT/A) has led to a higher incidence of neutralizing anti‐BoNT/A antibodies (ABAs). Because BoNT/A is known to inhibit sweating, here we report sudometry as a possibility for predicting the presence of ABA. Sixteen patients suffering from spasmodic torticollis were selected: in 2 patients, BoNT/A treatment continued to be effective, in 9 patients, the treatment effect was impaired, and in 5 patients, secondary treatment failure developed. BoNT/A (100 mouse units, Dysport; Ipsen Pharma, Berkshire, United Kingdom) was injected subcutaneously into the lateral calves. Sweating was visualized with iodine starch staining. In addition, quantitative sudomotor axon reflex testing was performed at the injection site. Individual ABA titers were determined with a mouse bioassay. Results of sudometry significantly correlated with the BoNT/A treatment success. The quantitative sudomotor axon reflex testing was 0.58 ± 0.63 fraction of the normal mean in patients with treatment failure, 0.18 ± 0.13 fraction of the normal mean in those who responded partially, and 0 in responders (p < 0.01). Accordingly, the areas of the anhidrotic skin after subcutaneous injections were 4.5 ± 10.3cm2, 32.7 ± 16.5cm2, and 62cm2 (p < 0.01). Discrimination analysis indicated that the presence of ABA (6 ABA‐positive and 10 ABA‐negative) could be predicted correctly in all patients from the results of sudometry. Therefore, sudometry is a useful tool for identifying patients with neutralizing ABAs and might be helpful for identifying reasons for BoNT/A treatment failure.

Überleben mit Heimbeatmung Eine offene, prospektive Untersuchung zur Heimbeatmung bei neuromuskulären Erkrankungen unter besonderer Berücksichtigung der Situation von ALS-Patienten

ZusammenfassungImmer mehr Patienten mit neuromuskulären Erkrankungen werden heimbeatmet. Euphorischen Berichten über die Methode stehen kritische bis ablehnende Haltungen vieler Ärzte gegenüber. Wir untersuchten prospektiv über einen Zeitraum von 6 Jahren den Langzeiteffekt, die Komplikationen und den Erkrankungsverlauf der Heimbeatmungsbehandlung von Patienten mit neuromuskulären Erkrankungen (NMK). In diesem Zeitraum wurden 31 Patienten über 17.517 Heimbeatmungstage beobachtet [im Mittel 565 (Min/Max: 30–2930) Tage]. 25 Patienten konnten nichtinvasiv mit verschieden Beatmungsmasken beatmet werden. Das mittlere Überleben mit Maskenbeatmung betrug bei Patienten mit stabilen NMK 2.052 (SE: ±317,8) Tage, bei ALS-Patienten ohne bulbäre Symptomatik 248 (±35,7) Tage, bei Bulbärparalyse 82 (±27,4) Tage. Bei maskenbeatmeten und tracheotomierten ALS-Patienten wurden im Vergleich zu nicht-invasiv beatmeten sNMK-Patienten signifikant mehr Komplikationen beobachtet. Diese Daten zeigen, dass die nicht-invasive Beatmung für Patienten mit stabilen oder langsam-progredienten neuromuskulären Erkrankungen über viele Jahre effektiv ist, Komplikationen sind selten. ALS-Patienten ohne bulbäre Symptomatik profitieren ebenfalls von dieser Beatmungsform, der Erfolg bei Patienten mit Bulbärparalyse ist deutlich geringer.SummaryA growing number of patients with neuromuscular disease have been treated with home mechanical ventilation during the past 15 years. We prospectively examined the long-term effects and complications of this method, particularly with regard to noninvasive positive pressure ventilation (NPPV). Thirty-one patients with amyotrophic lateral sclerosis (ALS, n=20) or other slowly progressive neuromuscular diseases (NMD, n=11) were observed for 17,517 home ventilation days (almost 48 ventilation years). The mean observed ventilation time was 565 days (min/max: 30/2930). Twenty-five patients were ventilated noninvasively with different masks. The calculated mean survival with NPPV ventilation (criteria: death, tracheostomy, or patient deciding to break off) was 2052 (SE: ±317.8) days in the NMD group, 248 days (±35.7) for ALS patients without bulbar symptoms, and 82 days (±27.4) with bulbar paralysis. Complications with the need for intervention were observed six times more frequently with ALS than with NMD. NPPV is effective for years in patients with slowly progressing NMD. Those ALS patients without bulbar symptoms can profit for up to a year from NPPV, while those with bulbar paralysis can have some symptom relief. Complications of every kind are much more frequent in ALS patients.

Botulinum-Neurotoxin in der Behandlung der Spastizität im Erwachsenenalter

Spasticity is one of the major causes of functional impairment in adults with lesions of the central nervous system. For instance, approximately 30% of post-stroke patients suffer from different degrees of spasticity with possible consecutive impairments. Numerous studies or meta-analyses showed that local injections of botulinum toxin in spastic muscles lead to dose-dependent reduction in muscle tone and improvement of passive movements (e. g. facilitated care), especially following repeated injections.However, country-specific regulations and patient-remote administration in German health care often do not allow adequate provision of this therapy. Thus, the present consensus statement based on the EBM analyses of the published international literature tries to highlight recent advances and the standard in the field of local spasticity treatment, aiming to facilitate communication between the decision makers and German reimbursement institutions in health care. Prior to initiation of BoNT-A injections, patient-oriented goals should be identified in a multiprofessional context to assure realistic goals for this specific treatment and patient expectations. In Germany for the treatment of focal spasticity following stroke three products have been approved: Botox® (Pharm Allergan, Ettlingen), Dysport® (Ipsen Pharma, Ettlingen) and Xeomin® (Merz Pharma, Frankfurt/Main). For all preparations safety has been repeatedly shown. Functional improvements have also been illustrated for selected patients concerning hand/arm function and gait. The dose per muscle and the selection of muscles to be injected have to be individualized according to the patients symptoms and should be accompanied by modern neurorehabilitative therapies such as redression or repetitive activation of the injected and antagonistic muscles.

Empfehlung zur Heim- und Langzeitbeatmung

partialdruck (PaO2) und/oder ein erhöhter arterieller Kohlendioxidpartialdruck (PaCO2) treten im Frühstadium von Erkrankungen zuerst im Schlaf, unter körperlicher Belastung oder im Liegen auf. Daher können tagsüber in Ruhe die arteriellen/kapillären Blutgaspartialdrücke normal sein. Eine kompensierte respiratorische Insuffizienz liegt vor, wenn die Sauerstoffsättigung nur durch eine erhebliche Hyperventilation im Normbereich gehalten werden kann und/oder wenn damit eine erhebliche Beanspruchung der Atmungsmuskulatur besteht bei noch normalem PaCO2. Die Störungen, die zur respiratorischen Insuffizienz führen, können an verschiedenen Stellen des respiratorischen Systems lokalisiert sein und unterschiedliche pathophysiologische Ursachen haben. Sie führen entweder primär zu einer Störung der Sauerstoffaufnahme (Versagen des Gasaustauschs, hypoxisches Versagen) oder zu einer Verminderung der alveolären Ventilation (ventilatorisches Versagen) mit sekundärer Hypoxämie.

SELTENE URSACHE EINES PERAKUTEN VISUSVERLUSTES : PSEUDOTUMOR CEREBRI : FALLBERICHT UBER VERLAUF MIT REZIDIV NACH DEKOMPRESSION DES N.OPTIKUS

ZusammenfassungBeim primären Pseudotumor cerebri liegt eine ätiopathogenetisch ungeklärte Hirndrucksteigerung vor, die sich klinisch in unterschiedlichen Verlaufsformen äußert. Die Therapie ist kontrovers. Es wird der Fall eines Verlaufs mit foudroyanter und schwerster Visusminderung sowie Rezidiv nach operativer einseitiger Optikusdekompression vorgestellt. Bei einer 30jährigen Patientin kam es innerhalb von 48 h zu Kopf- und Nackenschmerzen und perakuter Visusminderung auf 1/50 am RA und Wahrnehmung von Handbewegungen und Lichtschein am LA. Fundoskopisch bestand eine STP von 9 Dptr. beidseits. Der initialen Besserung aller Symptome nach operativer Dekompression des N. opticus folgte nach 3 Monaten ein Rezidiv. Eine 24-h-Hirndruckmessung zeigte erhöhte Werte. Nach Anlage eines ventrikuloperitonealen Shuntes kam es zur deutlichen, bis sechs Monate danach anhaltenden Befundbesserung. Der primäre PTC kann mit foudroyantem Visusminderung einhergehen. Bei unzureichender Wirksamkeit konservativer Therapien stehen unterschiedliche operative Verfahren (Optikusdekompression, Liquorshuntverfahren) zur Vefügung.SummaryIn primary pseudotumor cerebri (PTC) intracranial pressure is elevated by so far unknown mechanisms. There is a wide range of clinical courses. Therapy is controversial. We present a case of PTC with acute visual loss. After optic nerve sheath decompression a relapse occured. A 30-year old female patient experienced visual loss within 48 h accompanied by headache and slight neck stiffness. Visual acuity was 1/50 in the right eye; in the left eye just hand movements and light were perceived. Fundoscopy revealed a 9 dptr. prominent optic disc bilaterally. After optic nerve sheath decompression (ONSD) she improved, but underwent a relapse after 3 months. Twenty-four-hour measurement of intracranial pressure revealed elevated values. As a consequence ventriculo-peritoneal shunting was performed, leading to prominent improvement. Primary PTC can cause acute visual loss. If conservative treatment fails, different surgical procedures should be considered.