Isolated Hypoglossal Nerve Palsy as an Early Symptom of a Granular Cell Tumor.

BACKGROUND: Hypoglossal nerve palsy (HNP) is rather common as a neurological disease. However, as an isolated nerve palsy it is an exceedingly rare phenomenon and points at local pathologies along the peripheral course of the nerve. In this communication we report a granular cell tumor (GCT) arising in the submandibular segment of the hypoglossal nerve. CASE-REPORT: Spontaneous isolated HNP was recognized in a female patient. First line MR-imaging identified a clivus-chordoma. However, involvement of the hypoglossal nerve was highly unlikely according to MR-findings. Finally, ultrasonographic investigation revealed a small submandibular mass which, at histological examination, turned out to be a granular cell tumor arising within the hypoglossal nerve. CONCLUSIONS: This is the report of an extremely rare GCT originating within the 12th cranial nerve. The case illustrates that isolated motoric cranial nerve palsy may result from this rare tumor entity. This report also points out the diagnostic value of a simple ultrasonographic investigation to depict pathologic lesions of the submandibular space.

From discourse to pathology: Automatic identification of Parkinson's disease patients via morphological measures across three languages.

Embodied cognition research on Parkinson's disease (PD) points to disruptions of frontostriatal language functions as sensitive targets for clinical assessment. However, no existing approach has been tested for crosslinguistic validity, let alone by combining naturalistic tasks with machine-learning tools. To address these issues, we conducted the first classifier-based examination of morphological processing (a core frontostriatal function) in spontaneous monologues from PD patients across three typologically different languages. The study comprised 330 participants, encompassing speakers of Spanish (61 patients, 57 matched controls), German (88 patients, 88 matched controls), and Czech (20 patients, 16 matched controls). All subjects described the activities they perform during a regular day, and their monologues were automatically coded via morphological tagging, a computerized method that labels each word with a part-of-speech tag (e.g., noun, verb) and specific morphological tags (e.g., person, gender, number, tense). The ensuing data were subjected to machine-learning analyses to assess whether differential morphological patterns could classify between patients and controls and reflect the former's degree of motor impairment. Results showed robust classification rates, with over 80% of patients being discriminated from controls in each language separately. Moreover, the most discriminative morphological features were associated with the patients' motor compromise (as indicated by Pearson r correlations between predicted and collected motor impairment scores that ranged from moderate to moderate-to-strong across languages). Taken together, our results suggest that morphological patterning, an embodied frontostriatal domain, may be distinctively affected in PD across languages and even under ecological testing conditions.

[Deep brain stimulation in movement disorders: evidence and therapy standards]. / Tiefe Hirnstimulation bei Bewegungsstörungen: Evidenz und Therapiestandards.

The deep brain stimulation (DBS) in movement disorders is well established and in many aspects evidence-based procedure. The treatment indications are very heterogeneous and very specific in their course and therapy. The deep brain stimulation plays very important, but usually not the central role in this conditions. The success in the application of DBS is essentially associated with the correct, appropriate and timely indication of the therapy in the course of these diseases. Thanks to the good standardization of the DBS procedure and sufficient published data, the recommendations for indication, diagnosis and operative procedures can be generated. The following article attempts to summarize the most important decision-making criteria and current therapy standards in this fairly comprehensive subject and to present them in close proximity to practice.

Rho-associated protein kinase 2 (ROCK2): a new target of autoimmunity in paraneoplastic encephalitis.

Onconeural antibodies are associated with cancer and paraneoplastic encephalitis. While their pathogenic role is still largely unknown, their high diagnostic value is undisputed. In this study we describe the discovery of a novel target of autoimmunity in an index case of paraneoplastic encephalitis associated with urogenital cancer.A 75-year-old man with a history of invasive bladder carcinoma 6 years ago with multiple recurrences and a newly discovered renal cell carcinoma presented with seizures and progressive cognitive decline followed by super-refractory status epilepticus. Clinical and ancillary findings including brain biopsy suggested paraneoplastic encephalitis. Immunohistochemistry of the brain biopsy was used to characterize the inflammatory response. Indirect immunofluorescence assay (IFA) was used for autoantibody screening. The autoantigen was identified by histo-immunoprecipitation and mass spectrometry and was validated by expressing the recombinant antigen in HEK293 cells and neutralization tests. Sera from 125 control patients were screened using IFA to test for the novel autoantibodies.IFA analysis of serum revealed a novel autoantibody against brain tissue. An intracellular enzyme, Rho-associated protein kinase 2 (ROCK2), was identified as target-antigen. ROCK2 was expressed in affected brain tissue and archival bladder tumor samples of this patient. Brain histopathology revealed appositions of cytotoxic CD8+ T cells on ROCK2-positive neurons. ROCK2 antibodies were not found in the sera of 20 patients with bladder cancer and 17 with renal cancer, both without neurological symptoms, 49 healthy controls, and 39 patients with other antineuronal autoantibodies. In conclusion, novel onconeural antibodies targeting ROCK2 are associated with paraneoplastic encephalitis and should be screened for when paraneoplastic neurological syndromes, especially in patients with urogenital cancers, occur.

Postoperative neuroimaging analysis of DRT deep brain stimulation revision surgery for complicated essential tremor.

BACKGROUND: We report a patient who received conventional bilateral deep brain stimulation of the ventral intermediate nucleus of thalamus (Vim) for the treatment of medication refractory essential tremor (ET). After initial beneficial effects, therapeutic efficacy was lost due to a loss of control of his proximal trunkal and extremity tremor. The patient received successful diffusion tensor magnetic resonance imaging fiber tractographic (DTI FT)-assisted DBS revision surgery targeting the dentato-rubro-thalamic tract (DRT) in the subthalamic region (STR). OBJECTIVE: To report the concept of DTI FT-assisted DRT DBS revision surgery for ET and to show sophisticated postoperative neuroimaging analysis explaining improved symptom control. METHODS: Analysis was based on preoperative DTI sequences and postoperative helical computed tomography (hCT). Leads, stimulation fields, and fibers were reconstructed using commercial software systems (Elements, Brainlab AG, Feldkirchen, Germany; GUIDE XT, Boston Scientific Corp., Boston, MA, USA). RESULTS: The patient showed immediate and sustained tremor improvement after DTI FT-assisted revision surgery. Analysis of the two implantations (electrode positions in both instances) revealed a lateral and posterior shift in the pattern of modulation of the cortical fiber pathway projection after revision surgery as compared to initial implantation, explaining a more efficacious stimulation. CONCLUSIONS: Our work underpins a possible superiority of direct targeting approaches using advanced neuroimaging technologies to perform personalized DBS surgery. The evaluation of DBS electrode positions with the herein-described neuroimaging simulation technologies will likely improve targeting and revision strategies. Direct targeting with DTI FT-assisted approaches in a variety of indications is the focus of our ongoing research.

Is postoperative encephalopathy with choreoathetosis an acquired form of neuroacanthocytosis?

Postoperative encephalopathy with choreoathetosis ("postpump chorea") is a rare complication of open-heart surgery and, in particular, the employment of a cardiopulmonary bypass pump. It almost exclusively occurs in young children. While risk factors and the underlying histopathology have been identified, the pathogenesis of postpump chorea, crucially, remains largely unknown. Transient cerebral hypoperfusion associated with cardiopulmonary bypass is considered a likely candidate mechanism, but the evidence is insufficient and inconclusive. It is hypothesized in this article, that postpump chorea may be caused by mechanical trauma to red blood cells and resulting acanthocytosis. These dysfunctional erythrocytes could then lead to damage to the globus pallidus and disease development akin to that presumed in neuroacanthocytosis. In patients with neuroacanthocytosis an association between acanthocytosis and basal ganglia pathology has been suggested. To test the mechanism hypothesized here, the effects of cardiopulmonary bypass on erythrocyte morphology and function could be systematically tested in children undergoing cardiac surgery. Ideally, the extent of erythrocyte damage could be correlated with the risk of developing postpump chorea. Finally, if the proposed hypothesis is supported by empirical findings, efforts to reduce blood cell damage during extracorporeal circulation in children might prevent this devastating complication.

Two different phenomena in basic motor speech performance in premanifest Huntington disease.

OBJECTIVE: Dysarthria is a common feature in Huntington disease (HD). The aim of this cross-sectional pilot study was the description and objective analysis of different speech parameters with special emphasis on the aspect of speech timing of connected speech and nonspeech verbal utterances in premanifest HD (preHD). METHODS: A total of 28 preHD mutation carriers and 28 age- and sex-matched healthy speakers had to perform a reading task and several syllable repetition tasks. Results of computerized acoustic analysis of different variables for the measurement of speech rate and regularity were correlated with clinical measures and MRI-based brain atrophy assessment by voxel-based morphometry. RESULTS: An impaired capacity to steadily repeat single syllables with higher variations in preHD compared to healthy controls was found (variance 1: Cohen d = 1.46). Notably, speech rate was increased compared to controls and showed correlations to the volume of certain brain areas known to be involved in the sensory-motor speech networks (net speech rate: Cohen d = 1.19). Furthermore, speech rate showed correlations to disease burden score, probability of disease onset, the estimated years to onset, and clinical measures like the cognitive score. CONCLUSIONS: Measurement of speech rate and regularity might be helpful additional tools for the monitoring of subclinical functional disability in preHD. As one of the possible causes for higher performance in preHD, we discuss huntingtin-dependent temporarily advantageous development processes of the brain.

Characterization Methods for the Detection of Multiple Voice Disorders: Neurological, Functional, and Laryngeal Diseases.

This paper evaluates the accuracy of different characterization methods for the automatic detection of multiple speech disorders. The speech impairments considered include dysphonia in people with Parkinson's disease (PD), dysphonia diagnosed in patients with different laryngeal pathologies (LP), and hypernasality in children with cleft lip and palate (CLP). Four different methods are applied to analyze the voice signals including noise content measures, spectral-cepstral modeling, nonlinear features, and measurements to quantify the stability of the fundamental frequency. These measures are tested in six databases: three with recordings of PD patients, two with patients with LP, and one with children with CLP. The abnormal vibration of the vocal folds observed in PD patients and in people with LP is modeled using the stability measures with accuracies ranging from 81% to 99% depending on the pathology. The spectral-cepstral features are used in this paper to model the voice spectrum with special emphasis around the first two formants. These measures exhibit accuracies ranging from 95% to 99% in the automatic detection of hypernasal voices, which confirms the presence of changes in the speech spectrum due to hypernasality. Noise measures suitably discriminate between dysphonic and healthy voices in both databases with speakers suffering from LP. The results obtained in this study suggest that it is not suitable to use every kind of features to model all of the voice pathologies; conversely, it is necessary to study the physiology of each impairment to choose the most appropriate set of features.

Immunoglobulin-G4-related hypertrophic pachymeningitis with antineutrophil cytoplasmatic antibodies effectively treated with rituximab.

We describe a 52-year-old man with hypertrophic pachymeningitis (HP) who was both seropositive for antineutrophil cytoplasmatic antibodies (ANCA) against myeloperoxidase, and had an immunoglobulin G4 (IgG4) positive fibroinflammatory response in meningeal biopsy. HP is a chronic inflammatory thickening of the dura mater which typically presents with headache, cranial nerve dysfunction and other neurological deficits. While first-line treatment with corticosteroids is recommended, many patients relapse and need additional immunosuppression. One recently described etiology is IgG4-related disease and in a subgroup of idiopathic patients, evidence suggests a crucial role of ANCA. To our knowledge, the simultaneous occurrence of IgG4-related disease and ANCA has not been reported so far. This man suffered life-threatening disease progression despite the administration of high dose steroids, cyclophosphamide and azathioprine. Treatment with rituximab was initiated which led to disappearance of clinical symptoms and decrease of dural thickening within weeks. This patient presents a possible disease overlap of IgG4-related and ANCA-associated HP and illustrates the effectiveness of rituximab in refractory IgG4-related HP.

Phonatory dysfunction as a preclinical symptom of Huntington disease.

PURPOSE: Although dysphonia has been shown to be a common sign of Huntington disease (HD), the extent of phonatory dysfunction in gene positive premanifest HD individuals remains unknown. The aim of the current study was to explore the possible occurrence of phonatory abnormalities in prodromal HD. METHOD: Sustained vowel phonations were acquired from 28 premanifest HD individuals and 28 healthy controls of comparable age. Data were analysed acoustically for measures of several phonatory dimensions including airflow insufficiency, aperiodicity, irregular vibration of vocal folds, signal perturbations, increased noise, vocal tremor and articulation deficiency. A predictive model was built to find the best combination of acoustic features and estimate sensitivity/specificity for differentiation between premanifest HD subjects and controls. The extent of voice deficits according to a specific phonatory dimension was determined using statistical decision making theory. The results were correlated to global motor function, cognitive score, disease burden score and estimated years to disease onset. RESULTS: Measures of aperiodicity and increased noise were able to significantly differentiate between premanifest HD individuals and controls (p<0.01). The combination of these aspects of dysphonia led to a sensitivity of 91.5% and specificity of 79.2% to correctly distinguish speakers with premanifest HD from healthy individuals. Some form of disrupted phonatory function was revealed in 68% of our premanifest HD subjects, where 18% had one affected phonatory dimension and 50% showed impairment of two or more dimensions. A relationship between pitch control and cognitive score was also observed (r =  -0.50, p =  0.007). CONCLUSIONS: Phonatory abnormalities are detectable even the in premotor stages of HD. Speech investigation may have the potential to provide functional biomarkers of HD and could be included in future clinical trials and therapeutic interventions.

Effect of subthalamic stimulation on voice and speech in Parkinson's disease: for the better or worse?

BACKGROUND: Deep brain stimulation of the subthalamic nucleus, although highly effective for the treatment of motor impairment in Parkinson's disease (PD), can induce speech deterioration in a subgroup of patients. The aim of the current study was to survey (1) if there are distinctive stimulation effects on the different parameters of voice and speech and (2) if there is a special pattern of preexisting speech abnormalities indicating a risk for further worsening under stimulation. METHODS: N = 38 patients with PD had to perform a speech test without medication with stimulation ON (StimON) and stimulation OFF (StimOFF). Speech samples were analyzed: (1) according to a four-dimensional perceptual speech score and (2) by acoustic analysis to obtain quantifiable measures of distinctive speech parameters. RESULTS: Quality of voice was ameliorated with StimON, and there were trends of increased loudness and better pitch variability. N = 8 patients featured a deterioration of speech with StimON, caused by worsening of articulation or/and fluency. These patients already had more severe overall speech impairment with characteristic features of articulatory slurring and articulatory acceleration under StimOFF condition. CONCLUSION: The influence of subthalamic StimON Parkinsonian speech differs considerably between individual patients, however, there is a trend to amelioration of voice quality and prosody. Patients with stimulation-associated speech deterioration featured higher overall speech impairment and showed a distinctive pattern of articulatory abnormalities at baseline. Further investigations to confirm these preliminary findings are necessary to allow neurologists to pre-surgically estimate the individual risk of deterioration of speech under stimulation.

Impaired motor speech performance in Huntington's disease.

Dysarthria is a common symptom of Huntington's disease and has been reported, besides other features, to be characterized by alterations of speech rate and regularity. However, data on the specific pattern of motor speech impairment and their relationship to other motor and neuropsychological symptoms are sparse. Therefore, the aim of the present study was to describe and objectively analyse different speech parameters with special emphasis on the aspect of speech timing of connected speech and non-speech verbal utterances. 21 patients with manifest Huntington's disease and 21 age- and gender-matched healthy controls had to perform a reading task and several syllable repetition tasks. Computerized acoustic analysis of different variables for the measurement of speech rate and regularity generated a typical pattern of impaired motor speech performance with a reduction of speech rate, an increase of pauses and a marked disability to steadily repeat single syllables. Abnormalities of speech parameters were more pronounced in the subgroup of patients with Huntington's disease receiving antidopaminergic medication, but were also present in the drug-naïve patients. Speech rate related to connected speech and parameters of syllable repetition showed correlations to overall motor impairment, capacity of tapping in a quantitative motor assessment and some score of cognitive function. After these preliminary data, further investigations on patients in different stages of disease are warranted to survey if the analysis of speech and non-speech verbal utterances might be a helpful additional tool for the monitoring of functional disability in Huntington's disease.

Mechanical thrombectomy - an alternative treatment option in a patient with acute ischemic stroke and multiple contraindications for systemic thrombolysis: a case report.

INTRODUCTION: Acute ischemic stroke is a common cause of disability and death in developed countries. Standard therapy for patients who present within 4.5 hours from the onset of symptoms is intravenous thrombolysis if contraindications such as oral anticoagulation, cancer or recent surgery are ruled out. Apart from that, mechanical recanalization is a new treatment option for patients with occlusion of major cerebral arteries as a cause of ischemic stroke. CASE PRESENTATION: In this case report we describe a 55-year-old Caucasian man with a right hemispheric ischemic syndrome who presented in time but who had multiple contraindications against systemic thrombolysis. He was then treated with mechanical recanalization and recovered. On discharge from the hospital he had only a slight left-sided facial paresis and discrete impairment of motion smoothness in his left hand. CONCLUSION: We conclude that multimodal imaging should be performed in all patients with an acute onset of neurological symptoms suspicious of ischemic stroke, even if they have contraindications against an intravenous thrombolytic treatment.

Refractory epileptic seizures due to vitamin B6 deficiency in a patient with Parkinson's disease under duodopa® therapy.

Levodopa/carbidopa intestinal gel (LCIG) infusion for the treatment of advanced Parkinson's disease (PD) has been suspected to provoke polyneuropathy in conjunction with vitamin B6, B12 and folate deficiency and elevated homocysteine levels. We describe a PD patient under LCIG therapy developing refractory epileptic seizures obviously promoted by vitamin B6 deficiency.

Effect of deep brain stimulation on speech performance in Parkinson's disease.

Deep brain stimulation (DBS) has been reported to be successful in relieving the core motor symptoms of Parkinson's disease (PD) and motor fluctuations in the more advanced stages of the disease. However, data on the effects of DBS on speech performance are inconsistent. While there are some series of patients documenting that speech function was relatively unaffected by DBS of the nucleus subthalamicus (STN), other investigators reported on improvements of distinct parameters of oral control and voice. Though, these ameliorations of single speech modalities were not always accompanied by an improvement of overall speech intelligibility. On the other hand, there are also indications for an induction of dysarthria as an adverse effect of STN-DBS occurring at least in some patients with PD. Since a deterioration of speech function has more often been observed under high stimulation amplitudes, this phenomenon has been ascribed to a spread of current-to-adjacent pathways which might also be the reason for the sporadic observation of an onset of dysarthria under DBS of other basal ganglia targets (e.g., globus pallidus internus/GPi or thalamus/Vim). The aim of this paper is to review and evaluate reports in the literature on the effects of DBS on speech function in PD.

Novel APP/Aß mutation K16N produces highly toxic heteromeric Aß oligomers.

Here, we describe a novel missense mutation in the amyloid precursor protein (APP) causing a lysine-to-asparagine substitution at position 687 (APP770; herein, referred to as K16N according to amyloid-ß (Aß) numbering) resulting in an early onset dementia with an autosomal dominant inheritance pattern. The K16N mutation is located exactly at the α-secretase cleavage site and influences both APP and Aß. First, due to the K16N mutation APP secretion is affected and a higher amount of Aß peptides is being produced. Second, Aß peptides carrying the K16N mutation are unique in that the peptide itself is not harmful to neuronal cells. Severe toxicity, however, is evident upon equimolar mixture of wt and mutant peptides, mimicking the heterozygous state of the subject. Furthermore, Aß42 K16N inhibits fibril formation of Aß42 wild-type. Even more, Aß42 K16N peptides are protected against clearance activity by the major Aß-degrading enzyme neprilysin. Thus the mutation characterized here harbours a combination of risk factors that synergistically may contribute to the development of early onset Alzheimer disease.

Multimodal CT imaging and recanalizing therapy in acute ischemic stroke: retrospective analysis of a one-year single-center experience.

BACKGROUND: Recanalizing therapy in ischemic stroke is restricted to thrombolysis within 3 h. Multimodal imaging of vessel and parenchymal perfusion status may allow the extension of this time window. AIM: To retrospectively analyze treatment results of any recanalizing therapy in clinical practice. METHODS: Patients comprised three groups: 'standard' intravenous thrombolysis within 3 h; 'off-label' intravenous thrombolysis, and off-label interventional therapy. Recanalizing therapy was applied dependent on multimodal CT according to standardized pathways. Short-term clinical courses were analyzed. RESULTS: Of 543 patients (ischemic stroke, TIA), 68 (12.5%) received some type of recanalizing therapy. Of these, 47 (mean age 73.4, 24 female, mean symptom onset and hospital admission 62 min) received standard and 10 off-label thrombolysis (70.8, 6 female, 332 min), and 11 interventional therapy, mostly mechanical thrombectomy (mean age 62.5, 7 female, 186 min). Mean Δ short-term National Institutes of Health Stroke Scale (2-5 days) in these three groups were 3.7 ± 4.7, 3.9 ± 4.4, and 4.1 ± 5.8, respectively. The short-term clinical benefit was similar in the three groups. CONCLUSION: Off-label therapy is considered to have a higher risk of complications. However, if multimodal CT imaging of acute ischemic stroke is incorporated in everyday clinical decision-making, the rate of effective recanalizing procedures may be increased without an apparent negative effect on short-term outcome.

Impairment of vowel articulation as a possible marker of disease progression in Parkinson's disease.

PURPOSE: The aim of the current study was to survey if vowel articulation in speakers with Parkinson's disease (PD) shows specific changes in the course of the disease. METHOD: 67 patients with PD (42 male) and 40 healthy speakers (20 male) were tested and retested after an average time interval of 34 months. Participants had to read a given text as source for subsequent calculation of the triangular vowel space area (tVSA) and vowel articulation index (VAI). Measurement of tVSA and VAI were based upon analysis of the first and second formant of the vowels /α/, /i/and /u/ extracted from defined words within the text. RESULTS: At first visit, VAI values were reduced in male and female PD patients as compared to the control group, and showed a further decrease at the second visit. Only in female Parkinsonian speakers, VAI was correlated to overall speech impairment based upon perceptual impression. VAI and tVSA were correlated to gait impairment, but no correlations were seen between VAI and global motor impairment or overall disease duration. tVSA showed a similar reduction in the PD as compared to the control group and was also found to further decline between first and second examination in female, but not in male speakers with PD. CONCLUSIONS: Measurement of VAI seems to be superior to tVSA in the description of impaired vowel articulation and its further decline in the course of the disease in PD. Since impairment of vowel articulation was found to be independent from global motor function but correlated to gait dysfunction, measurement of vowel articulation might have a potential to serve as a marker of axial disease progression.