Tiefenhirnstimulation

Erstellt am 07 Mar 2018 21:22
Zuletzt geändert: 28 Oct 2020 12:32

In den letzten Jahren wurde vorgeschlagen, die Betroffenen auch invasiven operativen Verfahren zu unterziehen. Basierend auf strukturellen und funktionellen Bildgebungsstudien wurde in offenen Einzelfallserien die tiefe Hirnstimulation im Bereich des posterioren Hypothalamus durchgeführt. Überzeugende Effekte konnten dabei nicht vermittelt werden. In offenen Studien werden Besserungsraten zwischen 50 und 70 % berichtet. In einer bisher einzigen placebokontrollierten doppelblinden Studie konnte kein signifikanter Unterschied zwischen einer echten Stimulation und einer vorgetäuschten Stimulation beschrieben werden. Fatale Folgen mit tödlichen intrakraniellen Blutungen sind eingetreten. In öffentlich geführten Internettagebüchern werden katastrophale Verläufe von einzelnen Betroffenen dokumentiert. Hinzu kommen die hohen Kosten des Verfahrens von über 30.000 Euro und die aufwändige postoperative Behandlung. Aufgrund der derzeitigen Datenlage kann weder ein theoretisches Rationale noch eine praktische Begründung für die Anwendung der tiefen Hirnstimulation bei Clusterkopfschmerz nachvollzogen werden. Die bisherigen Daten begründeten keinen Platz in der Therapie von Clusterkopfschmerzen.

Bei bestimmten Patienten mit Parkinson oder Parkinson-ähnlichen Bewegungsstörungen, bei denen Medikamente nicht mehr ausreichend wirksam sind, kann eine Tiefenhirnstimulation (THST, deep-brain-stimulation, auch Hirnschrittmacher) helfen. Die Klinik für Neurochirurgie Jena gehört zu den wenigen Zentren Deutschlands, die eine tiefe Hirnstimulation durchführen.

Literatur

FINDINGS:
Between July, 2006, and November, 2009, 251 participants were recruited, of whom 127 were allocated medical therapy alone and 124 were assigned bilateral subthalamic stimulation plus medical therapy. At 2-year follow-up, the levodopa-equivalent dose was reduced by 39% (-363·3 mg/day [SE 41·8]) in individuals allocated bilateral subthalamic stimulation plus medical therapy and was increased by 21% (245·8 mg/day [40·4]) in those assigned medical therapy alone (p<0·0001). Neuropsychiatric fluctuations decreased with bilateral subthalamic stimulation plus medical therapy during 2-year follow-up (mean change -0·65 points [SE 0·15]) and did not change with medical therapy alone (-0·02 points [0·15]); the between-group difference in change from baseline was significant (p=0·0028). At 2 years, the Ardouin scale subscore for hyperdopaminergic behavioural disorders had decreased with bilateral subthalamic stimulation plus medical therapy (mean change -1·26 points [SE 0·35]) and had increased with medical therapy alone (1·12 points [0·35]); the between-group difference was significant (p<0·0001). Mean change from baseline at 2 years in the Ardouin scale subscore for hypodopaminergic behavioural disorders, the Starkstein Apathy Scale score, and the Beck Depression Inventory score did not differ between treatment groups. Antidepressants were stopped in 12 patients assigned bilateral subthalamic stimulation plus medical therapy versus four patients allocated medical therapy alone. Neuroleptics were started in nine patients assigned medical therapy alone versus one patient allocated bilateral subthalamic stimulation plus medical therapy. During the 2-year follow-up, two individuals assigned bilateral subthalamic stimulation plus medical therapy and one patient allocated medical therapy alone died by suicide.
INTERPRETATION:
In a large cohort with Parkinson's disease and early motor complications, better overall behavioural outcomes were noted with bilateral subthalamic stimulation plus medical therapy compared with medical therapy alone. The presence of hyperdopaminergic behaviours and neuropsychiatric fluctuations can be judged additional arguments in favour of subthalamic stimulation if surgery is considered for disabling motor complications.

Schlussfolgerung: Die THS ist ein etabliertes Verfahren zur Behandlung verschiedener neurologischer und psychiatrischer Erkrankungen. Sie wurde in die Leitlinien der Deutschen Gesellschaft für Neurologie (DGN) aufgenommen und gilt bei der fortgeschrittenen Parkinson-Erkrankung als Standardbehandlung. Es ist abzusehen, dass sich Effektivität und Sicherheit des Verfahrens durch aktuelle technische Entwicklungen bei Elektrodengeometrien sowie durch Anwendung neuer Bildgebungsverfahren verbessern werden. Wünschenswert wären kontrollierte Studien zur Erweiterung der Indikationen, speziell im psychiatrischen Bereich.

Risiken

Mögliche Alternativen

Although deep brain electrical stimulation can alleviate the motor symptoms of Parkinson disease (PD), just a small fraction of patients with PD can take advantage of this procedure due to its invasive nature. A significantly less invasive methodepidural spinal cord stimulation (SCS)has been suggested as an alternative approach for symptomatic treatment of PD. However, the mechanisms underlying motor improvements through SCS are unknown. Here, we show that SCS reproducibly alleviates motor deficits in a primate model of PD. Simultaneous neuronal recordings from multiple structures of the cortico-basal ganglia-thalamic loop in parkinsonian monkeys revealed abnormal highly synchronized neuronal activity within each of these structures and excessive functional coupling among them. SCS disrupted this pathological circuit behavior in a manner that mimics the effects caused by pharmacological dopamine replacement therapy or deep brain stimulation. These results suggest that SCS should be considered as an additional treatment option for patients with PD.

In clinical practice, deep brain stimulation (DBS) is effective for treatment of motor symptoms in Parkinson's disease (PD). However, the mechanisms have not been understood completely. There are some reports that electrical stimulation exerts neuroprotective effects on the central nervous system diseases including cerebral ischemia, head trauma, epilepsy and PD, although there are a few reports on neuroprotective effects of spinal cord stimulation (SCS). We investigated the neuroprotective effects of high cervical SCS on PD model of rats. Adult female Sprague-Dawley rats received hour-long SCS (2, 50 or 200 Hz) with an epidural electrode at C1-2 level for 16 consecutive days. At 2 days after initial SCS, 6-hydroxydopamine (6-OHDA) was injected into the right striatum of rats. Behavioral evaluations of PD symptoms were employed, including cylinder test and amphetamine-induced rotation test performed at 1 and 2 weeks after 6-OHDA injection. Animals were subsequently euthanized for immunohistochemical investigations. In order to explore neurotrophic and growth factor upregulation induced by SCS, another cohort of rats that received 50 Hz SCS was euthanized at 1 and 2 weeks after lesion for protein assays. Behavioral tests revealed that the number of amphetamine-induced rotations decreased in SCS groups. Immunohistochemically, tyrosine hydroxylase (TH)-positive fibers in the striatum were significantly preserved in SCS groups. TH-positive neurons in the substantia nigra pars compacta were significantly preserved in 50 Hz SCS group. The level of vascular endothelial growth factor (VEGF) was upregulated by SCS at 1 week after the lesion. These results suggest that high cervical SCS exerts neuroprotection in PD model of rats, at least partially by upregulation of VEGF. SCS is supposed to suppress or delay PD progression and might become a less invasive option for PD patients, although further preclinical and clinical investigations are needed to confirm the effectiveness and safety.

Dopamine replacement therapy is useful for treating motor symptoms in the early phase of Parkinson's disease, but it is less effective in the long term. Electrical deep-brain stimulation is a valuable complement to pharmacological treatment but involves a highly invasive surgical procedure. We found that epidural electrical stimulation of the dorsal columns in the spinal cord restores locomotion in both acute pharmacologically induced dopamine-depleted mice and in chronic 6-hydroxydopamine–lesioned rats. The functional recovery was paralleled by a disruption of aberrant low-frequency synchronous corticostriatal oscillations, leading to the emergence of neuronal activity patterns that resemble the state normally preceding spontaneous initiation of locomotion. We propose that dorsal column stimulation might become an efficient and less invasive alternative for treatment of Parkinson's disease in the future.

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