Elfriede Karner

Neuropsychological and psychiatric changes after deep brain stimulation for Parkinson's disease: a randomised, multicentre study.

BACKGROUND Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces motor symptoms in patients with Parkinsons disease (PD) and improves their quality of life; however, the effect of DBS on cognitive functions and its psychiatric side-effects are still controversial. To assess the neuropsychiatric consequences of DBS in patients with PD we did an ancillary protocol as part of a randomised study that compared DBS with the best medical treatment. METHODS 156 patients with advanced Parkinsons disease and motor fluctuations were randomly assigned to have DBS of the STN or the best medical treatment for PD according to the German Society of Neurology guidelines. 123 patients had neuropsychological and psychiatric examinations to assess the changes between baseline and after 6 months. The primary outcome was the comparison of the effect of DBS with the best medical treatment on overall cognitive functioning (Mattis dementia rating scale). Secondary outcomes were the effects on executive function, depression, anxiety, psychiatric status, manic symptoms, and quality of life. Analysis was per protocol. The study is registered at ClinicalTrials.gov, number NCT00196911. FINDINGS 60 patients were randomly assigned to receive STN-DBS and 63 patients to have best medical treatment. After 6 months, impairments were seen in executive function (difference of changes [DBS-best medical treatment] in verbal fluency [semantic] -4.50 points, 95% CI -8.07 to -0.93, Cohens d=-;0.4; verbal fluency [phonemic] -3.06 points, -5.50 to -0.62, -0.5; Stroop 2 naming colour error rate -0.37 points, -0.73 to 0.00, -0.4; Stroop 3 word reading time -5.17 s, -8.82 to -1.52, -0.5; Stroop 4 colour naming time -13.00 s, -25.12 to -0.89, -0.4), irrespective of the improvement in quality of life (difference of changes in PDQ-39 10.16 points, 5.45 to 14.87, 0.6; SF-36 physical 16.55 points, 10.89 to 22.21, 0.9; SF-36 psychological 9.74 points, 2.18 to 17.29, 0.5). Anxiety was reduced in the DBS group compared with the medication group (difference of changes in Beck anxiety inventory 10.43 points, 6.08 to 14.78, 0.8). Ten patients in the DBS group and eight patients in the best medical treatment group had severe psychiatric adverse events. INTERPRETATION DBS of the STN does not reduce overall cognition or affectivity, although there is a selective decrease in frontal cognitive functions and an improvement in anxiety in patients after the treatment. These changes do not affect improvements in quality of life. DBS of the STN is safe with respect to neuropsychological and psychiatric effects in carefully selected patients during a 6-month follow-up period. FUNDING German Federal Ministry of Education and Research (01GI0201).

Language Lateralization in Temporal Lobe Epilepsy: A Comparison between fMRI and the Wada Test

Summary:  Purpose: Recent studies have claimed that language functional magnetic resonance imaging (fMRI) can identify language lateralization in patients with temporal lobe epilepsy (TLE) and that fMRI‐based findings are highly concordant with the conventional assessment procedure of speech dominance, the intracarotid amobarbital test (IAT).

Number processing in posterior cortical atrophy--a neuropsycholgical case study.

Posterior cortical atrophy (PCA) is an uncommon syndrome of dementia with early onset, characterised by disorders of higher visual function, variable symptoms of Balints syndrome, visual agnosia, alexia, agraphia, finger agnosia, right-left disorientation and dyscalculia [Benson D. F., Davis R. J., & Snyder B. D. (1988). Posterior cortical atrophy. Archives of Neurology, 45, 789-793]. In a single case study specific numerical deficits were observed which may be predicted by parietal neurodegeneration (more pronounced on the right side; verified by SPECT). Besides impairments in all tasks involving visuo-spatial abilities (e.g., dot counting, analog number scale task), deficits appeared in tasks requiring access to an internal representation of numbers such as mental number bisection, approximation, estimation and semantic facts. In number comparison an increased distance effect was found. In simple arithmetic, a striking dissociation between operations was found-multiplication and addition facts being preserved at a superficial level, subtraction and division being severely impaired. The study confirms the close relation between spatial and numerical processing and highlights the modular organisation of the semantic system (number semantics impaired). Moreover, the study adds evidence about the clinical manifestation of the particular degenerative syndrome.

Number processing and basal ganglia dysfunction: a single case study.

Numerical processing has never been investigated in a case of Fahrs disease (FD) and only rarely in cases of basal ganglia dysfunction. The study describes the cognitive decline of a pre-morbidly high-functioning patient (medical doctor) affected by FD and his difficulties in number processing. A MRI scan revealed bilateral calcifications in the basal ganglia and a brain PET showed a massive reduction of glucose metabolism in the basal ganglia and both frontal lobes, but no other brain abnormalities. The patients cognitive deficits included impairments in problem solving, in cognitive set shifting and in mental flexibility, as well as in verbal memory. These deficits are attributed to the disruption of the dorsolateral prefrontal circuit involving the basal ganglia. In number processing, the patient showed a severe deficit in the retrieval of multiplication facts, deficits in all tasks of numerical problem solving and in the execution of complex procedures. Importantly, he also showed a dense deficit in conceptual knowledge, which concerned all test conditions and all operations. The findings confirm the predictions of the triple code model in so far, as a disruption of cortico-subcortical loops involving the basal-ganglia may lead to specific deficits in fact retrieval. However, no verbal deficit, as assumed in the triple code model and reported in similar cases, could be observed. The present findings further add to current knowledge on numerical processing, showing how fronto-executive dysfunction may disrupt conceptual understanding of arithmetic. This study shows that not only parietal lesions may lead to severe deficits in conceptual understanding, but that basal ganglia lesions leading to frontal dysfunction may have a devastating effect.

Risk factors for executive dysfunction after subthalamic nucleus stimulation in Parkinson's disease.

A slight decline in cognitive functions and especially in executive functioning after deep brain stimulation (DBS) of the nucleus subthalamicus (STN) in patients with Parkinsons disease (PD) has been described. This study evaluated baseline parameters that contribute to a deterioration of cognitive functioning after DBS. We analyzed data from the neuropsychological protocol in a randomized controlled study comparing DBS with best medical treatment (BMT). Change scores were calculated for the cognitive domains “global cognitive functioning,” “memory,” “working memory,” “attention,” and “executive function.” These domain‐specific change scores were correlated with previously defined preoperative parameters. Compared with the BMT group (63 patients), the STN‐DBS group (60 patients) showed a significant decline only in the domain executive function 6 months after DBS, which was significantly correlated with age, levodopa‐equivalence dosage (LED) and axial subscore of the UPDRS in the off‐medication state at baseline. Multiple regression analysis showed that these three factors explained, however, only about 23% of the variance. Patients with higher age, higher baseline LED, and/or higher axial subscore of the UPDRS at baseline have an increased risk for worsening of executive function after STN‐DBS. High scores of these factors might reflect an advanced stage of disease progression. As these baseline factors explained the variance of the change score executive function only to a minor proportion, other factors including the surgical procedure, the exact placement of the electrode or postsurgical management might be more relevant for a decline in executive functioning after STN‐DBS.

Knowing 7 × 8, but not the meaning of ‘elephant’: Evidence for the dissociation between numerical and non-numerical semantic knowledge

Patients affected by semantic dementia (SD) and other severe cognitive deficits may show preserved numerical skills, including the retrieval of multiplication facts from long-term memory. No studies so far specifically investigated the network of arithmetic facts in semantic dementia. Thus, it is unknown whether preserved multiplication in SD truly reflects intact semantic knowledge or preserved retrieval of verbal sequences (just as the recitation of rhymes or poems). In the present study a patient (SG) with SD underwent an extensive assessment of number processing and calculation abilities. In particular, multiplication knowledge was investigated through a series of computerised tasks (production task, multiple-choice task, number bisection task with multiplicative triplets, number-matching task). SG demonstrated excellent performance in all number processing and calculation tasks. In computerised tasks tapping multiplication fact knowledge, SG was as accurate and fast as healthy controls. Analyses on individual regression slopes indicated that SGs reaction time effects (problem-size effect, problem-difficulty effect, interference effects, and facilitation effect) were comparable to those found in controls in each task. These results add new evidence to the independence of numerical knowledge from other semantic information and provide further insight into the organisation of stored arithmetic knowledge.

Episodic ataxia type 2: phenotype characteristics of a novel CACNA1A mutation and review of the literature

Episodic ataxia type 2 (EA2) is an autosomal dominant inherited neurological disorder that is characterized by paroxysmal episodes of ataxia. The causative gene for EA2 is CACNA1A which codes for the alpha 1A subunit of the voltage-gated P/Q-type calcium channel (Cav2.1). We detected a novel point mutation in the CACNA1A gene in a large Austrian family. All ten affected family members harbored a heterozygous c.3089+2T>C nucleotide exchange in intron 19. In silico modeling demonstrated a loss of the splice site of exon 19 by the mutation, which most likely results in exon skipping without frameshifting or use of an alternative splice site. Clinically, the family exhibited frequent ataxic episodes accompanied by headache in some individuals, which showed a good treatment response to acetazolamide or aminopyridine. Interictal phenotype variability was high ranging from an unremarkable clinical examination to a progressive cerebellar syndrome. Detailed cognitive testing with standardized neuropsychological tests revealed specific deficits in various domains including memory, executive functions and visual abilities. Moreover, a striking coincidence of socio-phobic behavior and anxiety disorders was detected within this family, which interfered with activities of daily living and has to be taken in consideration in EA2 patient management. We here characterize the phenotype of this novel CACNA1A mutation, review the respective literature and discuss implications on diagnosis and patient management.

FAB-D: German version of the Frontal Assessment Battery

Executive dysfunction (ED) is a frequent consequence of neurological disorders, such as stroke, trauma or dementia, but also appears in normal aging. We developed a German version of the Frontal Assessment Battery (FAB-D), a short test which has previously been developed (Dubois et al., Neurology 55:1621–1626, 2000) to detect ED during bedside screening. A sample of 401 cognitively intact subjects aged 50–95 was tested with the FAB-D and several neuropsychological tests tapping executive functions, memory and calculation abilities. Aim of the study was to receive normative data for different age and educational groups, and to learn which tests predict performance on the FAB-D. We found clear effects of age and education; furthermore, FAB-D performance was predicted by other tests of executive functioning, but also by calculation and memory abilities. The present study reports data of healthy individuals and may be useful for comparing patients’ performance with a normative sample.

Acute encephalopathy after intravenous administration of valproate in non-convulsive status epilepticus.

Sir, We report a 45-year-old woman suffering from intractable generalized epilepsy (GE). She had absence seizures and former rare generalized tonic clonic seizures (GTCS) since the age of 10 years with an actual frequency of 1–3 absence seizures per month. Previous CT or MRI-scans were normal, interictal electroencephalograms (EEGs) showed generalized fast spike wave activity without any focal abnormalities concordant with the diagnosis of primary GE. She presented in our outpatient clinic in a state of psychomotor slowing, diminished responsiveness, slurred speech and eyelid blinking. An immediately performed video-EEG revealed continuous generalized spike wave and poly spike wave activity (see Fig. 1). Neuropsychological bedside testing showed extended psychomotor slowing and impairment of attention and auditory short-term memory. At the time of admission, the patient was treated with phenytoin 250 mg/day (serum level 16.5 lg/ml) and topiramate 300 mg/day (serum level 4.1 lg/ml). A non-convulsive status epilepticus (NCSE) was diagnosed and treated with 8 mg Lorazepam IV followed by 1000 mg valproat (VPA) IV within 30 min and a maintenance dose of 2000 mg VPA IV per day. Phenytoin was reduced to 100 mg/ day, topiramate was continued with 250 mg/day. Patients behaviour and EEG returned back to normal within 1 h. Subsequently, over the next 24 h, the patient developed a stuporous state with repeated vomiting and occurrence of GTCS followed by coma on day 2 of IV VPA treatment. EEG recording showed diffuse generalized slowing with high amplitude delta waves predominantly over the frontal regions (see Fig. 2). Serum levels of VPA and phenytoin were 29.0 and 8.8 lg/ ml, respectively. The CT-scan revealed diffuse swelling (data not shown). Cerebrospinal fluid (CSF) analysis revealed an elevated lactate level of 29.6 lg/ml (normal range 13–18.9 lg/ml) and no signs of infection. Serum analysis exhibited slightly elevated liver enzyme levels (GOT 97 U/l, range 10–35 U/l; c-GT 69 U/l, range 5–39 U/l; GPT was normal; myoglobin 446 lg/l, range 0–116 lg/l) and creatininkinase (1397 U/l, range 24–140 U/l) were elevated, but ammonium was within the normal range. Neurological findings in the stuporous patient were bilateral Babinski signs and synergistic stretching of the upper and – less pronounced – of the lower limbs but no focal signs. An acute IV VPA induced encephalopathy was diagnosed. Thus, administration of the drug was stopped immediately and the patient was transferred to the neurological intensive care unit. Due to elevated CSF and serum lactate levels a possible mitochondriopathy was suspected and 3 g L-carnitine was administered once daily. An aspiration pneumonia was treated with 1800 mg clindamycin IV and 6 g cefotiam IV daily. No further intervention was necessary, and the patient recovered completely within 48 h with normalized EEG and cerebral CT-scan (data not shown). VPA rarely induces encephalopathy after initiating VPA therapy as well as after long-term oral administration [1]. The cause of acute encephalopathy is yet to be elucidated, however, metabolic, toxic or intrinsic effects of VPA were accused as well as hyperammonemia [2,3].

Hippocampal formation involvement in a language-activation task in patients with mesial temporal lobe epilepsy

Summary:  Purpose: The study aims to explore the contribution of the hippocampal formation to the retained language‐comprehension network in patients with unilateral mesial temporal lobe epilepsy (TLE).