Neurology May 2012 Volume 78 Issue 21

Objective: To test whether 4 weeks of bilateral repetitive transcranial magnetic stimulation (rTMS) to the temporal or temporoparietal cortex is effective and safe in the treatment of chronic tinnitus.Methods: In this controlled 3-armed trial, 48 patients with chronic tinnitus were treated with 4 weeks (20 sessions) of bilateral continuous theta burst stimulation (cTBS) at the Tubingen University Hospital. They were randomized to stimulation above the temporal cortex, the temporoparietal cortex, or as sham condition behind the mastoid. Patients were masked for the stimulation condition. Tinnitus severity was assessed after 2 and primarily 4 weeks of treatment and at 3 months follow-up with the tinnitus questionnaire and by a tinnitus change score. Audiologic safety was monitored by pure-tone and speech audiometry after 2 and 4 weeks of cTBS.Results: Tinnitus severity was slightly reduced from baseline by a mean (SD) 2.6 (8.2) after sham, 2.4 (8.0) after temporoparietal, 2.2 (8.3) after temporal treatment of 16 patients each, but there was no significant difference between sham treatments and temporal (confidence interval [CI] -5.4 to +6.7) or temporoparietal cTBS (CI -5.9 to +6.3) or real cTBS (CI -7 to +5.1). Patients' global evaluation of tinnitus change after treatment did not indicate any effects. Audiologic measures were unaffected by treatment.Conclusions: Treating chronic tinnitus for 4 weeks by applying cTBS to the temporal or temporoparietal cortex of both hemispheres appears to be safe but not more effective than sham stimulation. However, these results are not to be generalized to all forms of rTMS treatments for tinnitus.Classification of Evidence: This study provides Class I evidence that bilateral cTBS is not effective in the treatment of chronic tinnitus.GLOSSARY: AMT: active motor thresholdANOVA: analysis of varianceCI: confidence intervalcTBS: continuous theta burst stimulationITT: intention to treatPLC: placeborTMS: repetitive transcranial magnetic stimulationSAC: secondary auditory cortexTAC: temporoparietal association cortexTQ: tinnitus questionnaire(C)2012 American Academy of Neurology

Objective: To identify a new genetic cause of distal hereditary motor neuropathy (dHMN), which is also known as a variant of Charcot-Marie-Tooth disease (CMT), in a Chinese family.Methods: We investigated a Chinese family with dHMN clinically, electrophysiologically, and genetically. We screened for the mutations of 28 CMT or related pathogenic genes using an originally designed microarray resequencing DNA chip.Results: Investigation of the family history revealed an autosomal dominant transmission pattern. The clinical features of the family included mild weakness and wasting of the distal muscles of the lower limb and foot deformity, without clinical sensory involvement. Electrophysiologic studies revealed motor neuropathy. MRI of the lower limbs showed accentuated fatty infiltration of the gastrocnemius and vastus lateralis muscles. All 4 affected family members had a heterozygous missense mutation c.2677G>A (p.D893N) of alanyl-tRNA synthetase (AARS), which was not found in the 4 unaffected members and control subjects.Conclusion: An AARS mutation caused dHMN in a Chinese family. AARS mutations result in not only a CMT phenotype but also a dHMN phenotype.GLOSSARY: AARS: alanyl-tRNA synthetaseCMT: Charcot-Marie-ToothdHMN: distal hereditary motor neuropathyMRC: Medical Research CouncilSCV: sensory nerve conduction velocity(C)2012 American Academy of Neurology

Objectives: To describe lesional diffusion-weighted imaging characteristics in a cohort of patients with biopsy-proven CNS inflammatory demyelinating disease (IDD) and compare diffusion characteristics of ring-enhancing CNS IDD lesions vs abscesses and tumors.Methods: Forty prebiopsy apparent diffusion coefficient (ADC) maps were reviewed from 30 patients with CNS IDD. Lesions were analyzed for size, T2-weighted (T2W) hypointense rim, enhancement, and ADC pattern. ADC patterns of CNS IDD ring-enhancing lesions were compared with a published cohort of 35 patients with ring-enhancing tumors and abscesses.Results: IDD lesions displayed a spectrum of peripheral ADC patterns at the lesion edge: restricted diffusion (low ADC), 33%; increased diffusion (high ADC), 60%; and normal diffusion (homogeneously isointense), 7%. Of biopsied lesions, 93% enhanced (ring, 52%; heterogeneous, 34%; homogeneous, 7%). A hypointense T2W rim was observed in 53%. A ring pattern on ADC (isointense or dark) was associated with T2W hypointense rims (p = 0.02) but not with ring enhancement. On serial imaging, 4 of 7 (57%) patients demonstrated changes in ADC patterns. Peripheral restriction was more common in IDD (p = 0.006) than in tumors or abscesses, whereas central restriction was only observed in abscesses. Restricted lesions in the same stage were more common in the non-IDD cohort (42% vs 20%), with a uniform restricted pattern seen only in abscesses.Conclusions: In ring-enhancing lesions, peripheral diffusion restriction is more common in IDD than in tumors/abscesses, whereas central restriction is more common among abscesses. Rapid ADC pattern changes in IDD probably reflect dynamic lesion evolution and may distinguish IDD from tumors.GLOSSARY: ADC: apparent diffusion coefficientBCS: Balo concentric sclerosisDWI: diffusion-weighted imagingEDSS: Expanded Disability Status ScaleIDD: inflammatory demyelinating diseaseIQR: interquartile rangeMS: multiple sclerosisT2W: T2-weighted(C)2012 American Academy of Neurology

Objective: Primary progressive aphasia (PPA) has been proposed to comprise 3 discrete clinical subtypes: semantic, agrammatic/nonfluent, and logopenic. Recent consensus recommendations suggest a diagnostic framework based primarily on clinical and neuropsychological findings to classify these variants. Our objective was to evaluate the extent to which patients with PPA would conform to the proposed tripartite system and whether the clustering pattern of elements of the linguistic profile suggests discrete clinical syndromes.Methods: A total of 46 patients with PPA were prospectively recruited to the Cambridge Longitudinal Study of PPA. Sufficient data were collected to assess all consensus-proposed diagnostic domains. By comparing patients' performances against those of 30 age- and education-matched healthy volunteers, z scores were calculated, and values of 1.5 SDs outside control participants' means were considered abnormal. Raw test scores were used to undertake a principal factor analysis to identify the clustering pattern of individual measures.Results: Of the patients, 28.3%, 26.1%, and 4.3% fitted semantic, nonfluent/agrammatic, and logopenic categories respectively, and 41.3% did not fulfill the diagnostic recommendations for any of the 3 proposed variants. There was no significant between-group difference in age, education, or disease duration. Furthermore, the outcome of the factor analysis was in keeping with discrete semantic and nonfluent/agrammatic syndromes but did not support a logopenic variant.Conclusion: Taken together, the results of this prospective data-driven study suggest that although a substantial proportion of patients with PPA have neither the semantic nor the nonfluent variants, they do not necessarily conform to a discrete logopenic variant.GLOSSARY: lvPPA: logopenic variant of primary progressive aphasianfvPPA: nonfluent/agrammatic variant of primary progressive aphasiaPPA: primary progressive aphasiasvPPA: semantic variant of primary progressive aphasia(C)2012 American Academy of Neurology

Objective: To assess prospectively the accuracy and precision of a method for noninvasive intracranial pressure (ICP) measurement compared with invasive gold standard CSF pressure measurement.Methods: Included were 62 neurologic patients (37 idiopathic intracranial hypertension, 20 multiple sclerosis, 1 Guillain-Barre syndrome, 1 polyneuropathy, and 3 hydrocephalus). The average age was 40 +/- 12 years. All patients had lumbar puncture indicated as a diagnostic procedure. ICP was measured using a noninvasive ICP measurement method, which is based on a two-depth high-resolution transcranial Doppler insonation of the ophthalmic artery (OA). The OA is being used as a natural pair of scales, in which the intracranial segment of the OA is compressed by ICP and the extracranial segment of the OA is compressed by extracranial pressure (Pe) applied to the orbit. The blood flow parameters in both OA segments are approximately the same in the scales balance case when Pe = ICP. All patients had simultaneous recording of noninvasive ICP values and invasive gold standard CSF pressure values.Results: Analysis of the 72 simultaneous paired recordings of noninvasive ICP and the gold standard CSF pressure showed good accuracy for the noninvasive method as indicated by the low mean systematic error (0.12 mm Hg; confidence level [CL] 0.98). The method also showed high precision as indicated by the low SD of the paired recordings (2.19 mm Hg; CL 0.98). The method does not need calibration.Conclusion: The proposed noninvasive ICP measurement method is precise and accurate compared with gold standard CSF pressure measured via lumbar puncture.GLOSSARY: ABP: arterial blood pressureCL: confidence levelICP: intracranial pressureIOA: intracranial segment of the internal ophthalmic arteryMS: multiple sclerosisnICP: noninvasive intracranial pressureOA: ophthalmic arteryTBI: traumatic brain injuryTCD: transcranial Doppler(C)2012 American Academy of Neurology