Mohammad Maarouf

Unilateral deep brain stimulation of the nucleus accumbens in patients with treatment-resistant obsessive-compulsive disorder: Outcomes after one year.

OBJECTIVE To investigate the effects of unilateral deep brain stimulation (DBS) in the right nucleus accumbens in patients with obsessive-compulsive disorder (OCD). Predominantly bilateral stimulation of the anterior limb of the internal capsule was utilized. METHODS The study was designed as a double-blind sham-controlled crossover study. Patients received 3 months of deep brain stimulation followed by 3 months of sham stimulation, or vice versa. Subsequently, stimulation was continued unblinded for all patients. The primary outcome measure was the severity level of OCD, measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Secondary outcome measures were depressive symptoms, anxiety, psychological symptom severity, global functioning, quality of life, and cognitive function. RESULTS The mean Y-BOCS scores decreased significantly from 32.2 (+/-4.0) at baseline to 25.4 (+/-6.7) after 12 months (p=0.012). Five out of ten patients showed a decrease of more than 25%, indicating at least a partial response. One patient showed a decrease in Y-BOCS severity greater than 35%. Similarly, depression, global functioning and quality of life improved within one year. In contrast, anxiety, global symptom severity and cognitive function showed no significant changes. In general, DBS was well-tolerated. CONCLUSIONS DBS of the unilateral right nucleus accumbens showed encouraging results in patients with treatment-resistant OCD. Five out of ten patients reached at least a partial response after the first year.

Deep-brain stimulation: long-term analysis of complications caused by hardware and surgery—experiences from a single centre

Objective: To determine the surgery-related and hardware-related complications of deep-brain stimulation (DBS) at a single centre. Methods: 262 consecutive patients (472 electrodes) operated for DBS in our department from February 1996 to March 2003 were retrospectively analysed to document acute adverse events (30 days postoperatively). The data of 180 of these patients were additionally revised to assess long-term complications (352 electrodes, mean follow-up 36.3 (SD 20.8) months). Results: The frequency of minor intraoperative complications was 4.2% (11/262 patients). Transient (0.2%) or permanent (0.4%) neurological deficits, and in one case asymptomatic intracranial haemorrhage (0.2%), were registered as acute severe adverse events caused by surgery. Among minor acute complications were subcutaneous bleeding along the extension wire (1.2%) and haematoma at the pulse generator implantation site (1.2%). Skin infection caused by the implanted material was registered in 15 of 262 patients (5.7%). The infection rate during the first observation period was 1.5% (4/262 patients) and the late infection rate was 6.1% (11/180 patients). Partial or complete removal of the stimulation system was necessitated in 12 of 262 (4.6%) patients because of skin infection. During the long-term observation period, hardware-related problems were registered in 25 of 180 (13.9%) patients. Conclusions: Stereotactic implantation of electrodes for DBS, if performed with multiplanar three-dimensional imaging and advanced treatment planning software, is a safe procedure with no mortality and low morbidity. The main causes for the patients’ prolonged hospital stay and repeated surgery were wound infections and hardware-related complications.

Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer's dementia

Cholinergic neurons of the medial forebrain are considered important contributors to brain plasticity and neuromodulation. A reduction of cholinergic innervation can lead to pathophysiological changes of neurotransmission and is observed in Alzheimer’s disease. Here we report on six patients with mild to moderate Alzheimer’s disease (AD) treated with bilateral low-frequency deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM). During a four-week double-blind sham-controlled phase and a subsequent 11-month follow-up open label period, clinical outcome was assessed by neuropsychological examination using the Alzheimer’s Disease Assessment Scale—cognitive subscale as the primary outcome measure. Electroencephalography and [18F]-fluoro-desoxyglucose positron emission tomography were, besides others, secondary endpoints. On the basis of stable or improved primary outcome parameters twelve months after surgery, four of the six patients were considered responders. No severe or non-transitional side effects related to the stimulation were observed. Taking into account all limitations of a pilot study, we conclude that DBS of the NBM is both technically feasible and well tolerated.

Linear accelerator radiosurgery for pituitary macroadenomas: a 7-year follow-up study.

A prospective study was conducted to assess the efficacy and side effects of linear accelerator (LINAC)‐based radiosurgery (RS) performed with a reduced dose of therapeutic radiation for patients with surgically inaccessible pituitary macroadenomas.

Linac radiosurgery versus whole brain radiotherapy for brain metastases. A survival comparison based on the RTOG recursive partitioning analysis.

Background and Purpose:For patients with inoperable brain metastases, whole brain radiotherapy (WBRT) has been the standard treatment for decades. Radiosurgery is an effective alternative strategy, but has failed to show a substantial survival benefit so far. The prognostic factors derived from the RTOG recursive partitioning analysis (RPA) provide a framework that allows a nonrandomized comparison of the two modalities.Patients and Methods:From 1991 to 1998, 117 patients with one to three previously untreated cerebral metastases underwent single-dose linac radiosurgery (median dose 20 Gy) without adjuvant WBRT. After radiosurgery, 26/117 patients (22%) had salvage WBRT, radiosurgery or neurosurgical resection of recurrent (4/117) and/or new (24/117) metastases. Survival of these patients was compared to a historical group of 138 patients with one to three lesions treated by WBRT (30–36 Gy/3-Gy fractions) from 1978 to 1991; only nine of these patients (7%) had salvage WBRT. All patients were classified into the three RPA prognostic classes based on age, performance score, and presence of extracranial tumor manifestations.Results:In RPA class I (Karnofsky performance score ≥ 70, primary tumor controlled, no other metastases, age < 65 years), radiosurgery resulted in a median survival of 25.4 months (n = 23, confidence interval [CI] 5.8–45.0) which was significantly longer than for WBRT (n = 9, 4.7 months, CI 3.8–5.5; p < 0.0001). In RPA class III (Karnofsky performance score < 70), no significant difference in survival between radiosurgery (n = 20, 4.2 months, CI 3.2–5.3) and WBRT (n = 68, 2.5 months, CI 2.2–2.8) was found. In RPA class II (all other patients), radiosurgery produced a small, but significant survival advantage (radiosurgery: n = 74, 5.9 months, CI 3.2–8.5, WBRT: n = 61, 4.1 months, CI 3.4–4.9; p < 0.04).Conclusion:Radiosurgery in patients with one to three cerebral metastases results in a substantial survival benefit only in younger patients with a low systemic tumor burden when compared to WBRT alone. It cannot be excluded that this effect is partially caused by the available salvage options after radiosurgery.Hintergrund und Ziel:Für Patienten mit inoperablen Hirnmetastasen ist die Ganzhirnbestrahlung (WBRT) seit Jahrzehnten die Standardtherapie. Die Radiochirurgie stellt eine effektive Therapiealternative dar, jedoch wurde bisher kein eindeutiger Überlebensvorteil nachgewiesen. Die Risikogruppen der rekursiven Partitionsanalyse (RPA) der RTOG ermöglichen einen sinnvollen, nicht randomisierten Vergleich von WBRT und Radiochirurgie.Patienten und Methodik:Von 1991 bis 1998 erhielten 117 nicht vorbehandelte Patienten mit ein bis drei Hirnmetastasen eine Linac-Radiochirurgie (mediane Dosis 20 Gy) ohne adjuvante WBRT. Zusätzlich wurden 26/117 Patienten (22%) wegen eines lokalen Metastasenrezidivs (4/117) oder neu aufgetretener Hirnmetastasen (24/117) erneut mittels Radiochirurgie, WBRT oder neurochirurgischer Resektion behandelt. Das Überleben dieser Patienten wurde mit einer historischen Gruppe verglichen (n = 138), die von 1978 bis 1991 bei ein bis drei Hirnmetastasen eine alleinige Ganzhirnbestrahlung (30–36 Gy/3-Gy-Fraktionen) erhielt. Hiervon wurden nur neun Patienten (7%) wegen eines Rezidivs erneut mit einer WBRT behandelt. Alle Patienten wurden entsprechend ihrem Alter, dem Allgemeinzustand (Karnofsky-Index) und der Präsenz extrakranieller Tumormanifestationen in die drei RPA-Klassen eingeteilt.Ergebnisse:In der RPA-Klasse I (Karnofsky-Index ≥ 70, Primärtumor kontrolliert, keine weiteren Metastasen, Alter < 65 Jahre) führte die Radiochirurgie zu einem medianen Überleben von 25,4 Monaten (n = 23, Konfidenzintervall [CI] 5,8–45,0) und war somit der WBRT signifikant überlegen (n = 9, 4,7 Monate, CI 3,8–5,5; p < 0,0001). In der RPA-Klasse III (Karnofsky-Index < 70) ließ sich kein signifikanter Vorteil der Radiochirurgie (n = 20, 4,2 Monate, CI 3,2–5,3) gegenüber der WBRT (n = 68, 2,5 Monate, CI 2,2–2,8) nachweisen. In der RPA-Risikoklasse II (alle anderen Patienten) führte die Radiochirurgie nur zu einem geringen, aber signifikanten Überlebensvorteil (Radiochirurgie: n = 74, 5,9 Monate, CI 3,2–8,5, WBRT: n = 61, 4,1 Monate, CI 3,4–4,9; p < 0,04).Schlussfolgerung:Im Vergleich zur alleinigen WBRT führt die Radiochirurgie bei Patienten mit ein bis drei Hirnmetastasen nur in jüngerem Alter und bei geringer systemischer Tumorausbreitung zu einer Prognoseverbesserung. Möglicherweise spielt hierfür die höhere Verfügbarkeit von Salvage-Therapien eine Rolle.

Coordinated reset neuromodulation for Parkinson's disease: proof-of-concept study.

The discovery of abnormal synchronization of neuronal activity in the basal ganglia in Parkinsons disease (PD) has prompted the development of novel neuromodulation paradigms. Coordinated reset neuromodulation intends to specifically counteract excessive synchronization and to induce cumulative unlearning of pathological synaptic connectivity and neuronal synchrony.

Characterisation of tremor-associated local field potentials in the subthalamic nucleus in Parkinson's disease.

We simultaneously recorded local field potentials (LFPs) in the subthalamic nucleus (STN) and surface electromyographic signals (EMGs) from the extensor and flexor muscles of the contralateral forearm in eight patients with idiopathic tremor‐dominant Parkinson’s disease (resting tremor) during the bilateral implantation of deep brain stimulation electrodes. Recordings were made at different heights (in 0.5‐ to 2.0‐mm steps beginning outside the STN) using up to five concentrically configured macroelectrodes (2 mm apart). The patients were instructed to relax their contralateral forearm (rest condition). We analysed the coherence between tremor EMGs and STN LFPs, which showed significant tremor‐associated coupling at single tremor and double tremor frequencies. Moreover, the EMG–LFP coherences were characterised by differences between antagonistic muscles (flexor, extensor) and by the spatial distribution of LFPs within the STN. Coherence at single and double tremor frequencies occurred significantly more frequently within STN than above STN (in the zona incerta). In this study, we were able to show that, within STN, tremor‐associated LFP activity varied with spatial distribution and with the contralateral antagonistic forearm muscles. These findings suggest the existence of distribution‐ and muscle‐specific tremor‐associated LFP activity at different tremor frequencies and an organisation of tremor‐related subloops within the STN.

Linac Radiosurgery Versus Whole Brain Radiotherapy for Brain Metastases

Background and Purpose:For patients with inoperable brain metastases, whole brain radiotherapy (WBRT) has been the standard treatment for decades. Radiosurgery is an effective alternative strategy, but has failed to show a substantial survival benefit so far. The prognostic factors derived from the RTOG recursive partitioning analysis (RPA) provide a framework that allows a nonrandomized comparison of the two modalities.Patients and Methods:From 1991 to 1998, 117 patients with one to three previously untreated cerebral metastases underwent single-dose linac radiosurgery (median dose 20 Gy) without adjuvant WBRT. After radiosurgery, 26/117 patients (22%) had salvage WBRT, radiosurgery or neurosurgical resection of recurrent (4/117) and/or new (24/117) metastases. Survival of these patients was compared to a historical group of 138 patients with one to three lesions treated by WBRT (30–36 Gy/3-Gy fractions) from 1978 to 1991; only nine of these patients (7%) had salvage WBRT. All patients were classified into the three RPA prognostic classes based on age, performance score, and presence of extracranial tumor manifestations.Results:In RPA class I (Karnofsky performance score ≥ 70, primary tumor controlled, no other metastases, age < 65 years), radiosurgery resulted in a median survival of 25.4 months (n = 23, confidence interval [CI] 5.8–45.0) which was significantly longer than for WBRT (n = 9, 4.7 months, CI 3.8–5.5; p < 0.0001). In RPA class III (Karnofsky performance score < 70), no significant difference in survival between radiosurgery (n = 20, 4.2 months, CI 3.2–5.3) and WBRT (n = 68, 2.5 months, CI 2.2–2.8) was found. In RPA class II (all other patients), radiosurgery produced a small, but significant survival advantage (radiosurgery: n = 74, 5.9 months, CI 3.2–8.5, WBRT: n = 61, 4.1 months, CI 3.4–4.9; p < 0.04).Conclusion:Radiosurgery in patients with one to three cerebral metastases results in a substantial survival benefit only in younger patients with a low systemic tumor burden when compared to WBRT alone. It cannot be excluded that this effect is partially caused by the available salvage options after radiosurgery.Hintergrund und Ziel:Für Patienten mit inoperablen Hirnmetastasen ist die Ganzhirnbestrahlung (WBRT) seit Jahrzehnten die Standardtherapie. Die Radiochirurgie stellt eine effektive Therapiealternative dar, jedoch wurde bisher kein eindeutiger Überlebensvorteil nachgewiesen. Die Risikogruppen der rekursiven Partitionsanalyse (RPA) der RTOG ermöglichen einen sinnvollen, nicht randomisierten Vergleich von WBRT und Radiochirurgie.Patienten und Methodik:Von 1991 bis 1998 erhielten 117 nicht vorbehandelte Patienten mit ein bis drei Hirnmetastasen eine Linac-Radiochirurgie (mediane Dosis 20 Gy) ohne adjuvante WBRT. Zusätzlich wurden 26/117 Patienten (22%) wegen eines lokalen Metastasenrezidivs (4/117) oder neu aufgetretener Hirnmetastasen (24/117) erneut mittels Radiochirurgie, WBRT oder neurochirurgischer Resektion behandelt. Das Überleben dieser Patienten wurde mit einer historischen Gruppe verglichen (n = 138), die von 1978 bis 1991 bei ein bis drei Hirnmetastasen eine alleinige Ganzhirnbestrahlung (30–36 Gy/3-Gy-Fraktionen) erhielt. Hiervon wurden nur neun Patienten (7%) wegen eines Rezidivs erneut mit einer WBRT behandelt. Alle Patienten wurden entsprechend ihrem Alter, dem Allgemeinzustand (Karnofsky-Index) und der Präsenz extrakranieller Tumormanifestationen in die drei RPA-Klassen eingeteilt.Ergebnisse:In der RPA-Klasse I (Karnofsky-Index ≥ 70, Primärtumor kontrolliert, keine weiteren Metastasen, Alter < 65 Jahre) führte die Radiochirurgie zu einem medianen Überleben von 25,4 Monaten (n = 23, Konfidenzintervall [CI] 5,8–45,0) und war somit der WBRT signifikant überlegen (n = 9, 4,7 Monate, CI 3,8–5,5; p < 0,0001). In der RPA-Klasse III (Karnofsky-Index < 70) ließ sich kein signifikanter Vorteil der Radiochirurgie (n = 20, 4,2 Monate, CI 3,2–5,3) gegenüber der WBRT (n = 68, 2,5 Monate, CI 2,2–2,8) nachweisen. In der RPA-Risikoklasse II (alle anderen Patienten) führte die Radiochirurgie nur zu einem geringen, aber signifikanten Überlebensvorteil (Radiochirurgie: n = 74, 5,9 Monate, CI 3,2–8,5, WBRT: n = 61, 4,1 Monate, CI 3,4–4,9; p < 0,04).Schlussfolgerung:Im Vergleich zur alleinigen WBRT führt die Radiochirurgie bei Patienten mit ein bis drei Hirnmetastasen nur in jüngerem Alter und bei geringer systemischer Tumorausbreitung zu einer Prognoseverbesserung. Möglicherweise spielt hierfür die höhere Verfügbarkeit von Salvage-Therapien eine Rolle.

The causal relationship between subcortical local field potential oscillations and Parkinsonian resting tremor

To study the dynamical mechanism which generates Parkinsonian resting tremor, we apply coupling directionality analysis to local field potentials (LFP) and accelerometer signals recorded in an ensemble of 48 tremor epochs in four Parkinsonian patients with depth electrodes implanted in the ventro-intermediate nucleus of the thalamus (VIM) or the subthalmic nucleus (STN). Apart from the traditional linear Granger causality method we use two nonlinear techniques: phase dynamics modelling and nonlinear Granger causality. We detect a bidirectional coupling between the subcortical (VIM or STN) oscillation and the tremor, in the theta range (around 5 Hz) as well as broadband (>2 Hz). In particular, we show that the theta band LFP oscillations definitely play an efferent role in tremor generation, while beta band LFP oscillations might additionally contribute. The brain-->tremor driving is a complex, nonlinear mechanism, which is reliably detected with the two nonlinear techniques only. In contrast, the tremor-->brain driving is detected with any of the techniques including the linear one, though the latter is less sensitive. The phase dynamics modelling (applied to theta band oscillations) consistently reveals a long delay in the order of 1-2 mean tremor periods for the brain-->tremor driving and a small delay, compatible with the neural transmission time, for the proprioceptive feedback. Granger causality estimation (applied to broadband signals) does not provide reliable estimates of the delay times, but is even more sensitive to detect the brain-->tremor influence than the phase dynamics modelling.

Stereotactic linear accelerater-based radiosurgery for the treatment of patients with glomus jugulare tumors

The optimal treatment for patients with glomus jugulare tumor (GJT) of the skull base remains controversial. Surgical excision is associated with a high incidence of cranial nerve injury, decreased quality of life, and high mortality. Fractionated radiotherapy is used to control the majority of these tumors, but disadvantages are a prolonged therapy interval and exposition of adjacent brain tissue to irradiation. The authors present the results of a study on 12 of 14 consecutively admitted patients who were treated using linear accelerator‐based radiosurgery (LINAC‐RS), an innovative method for the treatment of GJT.