Intermittent theta burst stimulation (iTBS) versus 10 Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) to alleviate treatment-resistant unipolar depression: A randomized controlled trial (THETA-DEP).

BACKGROUND: Recently intermittent theta burst stimulation (iTBS) proved to be non-inferior to conventional repetitive transcranial magnetic stimulation (10 Hz rTMS) in unipolar depression after failure of one antidepressant trial, but to date no randomized control trial assessed the ability of iTBS to improve depression level and quality of life in more resistant features of depression with a long-term (6 month) follow-up in comparison to 10 Hz rTMS. OBJECTIVES/HYPOTHESIS: The aim of our study was to compare the efficacy of 10 Hz rTMS and iTBS in treatment-resistant unipolar depression on response rates (50% decrease of MADRS scores at one month from baseline) and change in quality of life during a 6-month follow-up. In addition, we investigated whether some clinical features at baseline were associated with the response in the different groups. METHOD: Sixty patients were randomized in a double-blind, controlled study at the University Hospital Center of Nantes, and received 20 sessions of either rTMS or iTBS applied to the left dorsolateral prefrontal cortex targeted by neuronavigation. Statistical analysis used Fischer's exact test and Chi-square test as appropriate, linear mixed model, and logistic regression (occurrence of depressive relapse and factors associated with the therapeutic response). RESULTS: Included patients showed in mean more than 3 antidepressants trials. Response rates were 36.7% and 33.3%, and remission rates were 18.5% and 14.8%, in the iTBS and 10 Hz rTMS groups respectively. Both groups showed a similar significant reduction in depression scores and quality of life improvement at 6 months. We did not find any clinical predictive factor of therapeutic response in this sample. CONCLUSION: Our study suggests the clinical interest of iTBS stimulation (which is more time saving and cost-effective as conventional rTMS) to provide long-lasting improvement of depression and quality of life in highly resistant unipolar depression.

Transient perivascular inflammation of the carotid artery (TIPIC) syndrome.

Background: The Transient Perivascular Inflammation of the Carotid artery (TIPIC) syndrome is presumably a very rare disease characterized by a local transient inflammation of the tissue around the carotid artery. Its pathophysiology remains unknown. We performed an updated study of TIPIC syndrome cases in the setting of a multinational collaborative study. Methods: This study was conducted as an observational multinational retrospective individual patient level cohort study. Information from all known cases diagnosed with TIPIC syndrome in the literature (2005-2020) was collected after a semi-structured literature search of PubMed and Web of Science. We also collected unpublished information of patients from French, Swiss, and Italian vascular medicine or radiology departments. Results: A total of 72 patients were included and served for data analysis: 42 (58.3%) were women; the mean age was 47.9 (SD=11.4) years. Symptoms were unilateral in 92% of patients and 81.4% required pain killers. At baseline, irrespective of the imaging method used, the median thickness of the carotid lesions was 5 (Q1-Q3: 4-7; range: 2-11) mm and the median length of the lesion was 20 (Q1-Q3: 10-30; range: 3-50) mm. We found a positive linear correlation between thickness and length. At follow-up, the thickness of the carotid lesions decreased to a median of 2 (Q1-Q3: 1-3; range: 0-6) mm; the length decreased to a median 10 (Q1-Q3: 5-15; range: 0-41) mm. A linear correlation between baseline and follow-up values was observed for both thickness and length measurements. Symptoms disappeared after a median of 14 (Q1-Q3: 10-15) days. Thirteen patients experienced a recurrence after a median follow-up of 6 (Q1-Q3: 2-12) months. Conclusions: The present analysis elucidates clinical and sonographic characteristics of TIPIC syndrome, indicating the benign nature of this condition. A future international registry will study the long-term course of the disease.

Efficacy of intermittent Theta Burst Stimulation (iTBS) and 10-Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant unipolar depression: study protocol for a randomised controlled trial.

BACKGROUND: The treatment of depression remains a challenge since at least 40% of patients do not respond to initial antidepressant therapy and 20% present chronic symptoms (more than 2 years despite standard treatment administered correctly). Repetitive transcranial magnetic stimulation (rTMS) is an effective adjuvant therapy but still not ideal. Intermittent Theta Burst Stimulation (iTBS), which has only been used recently in clinical practice, could have a faster and more intense effect compared to conventional protocols, including 10-Hz high-frequency rTMS (HF-rTMS). However, no controlled study has so far highlighted the superiority of iTBS in resistant unipolar depression. METHODS/DESIGN: This paper focuses on the design of a randomised, controlled, double-blind, single-centre study with two parallel arms, carried out in France, in an attempt to assess the efficacy of an iTBS protocol versus a standard HF- rTMS protocol. Sixty patients aged between 18 and 75 years of age will be enrolled. They must be diagnosed with major depressive disorder persisting despite treatment with two antidepressants at an effective dose over a period of 6 weeks during the current episode. The study will consist of two phases: a treatment phase comprising 20 sessions of rTMS to the left dorsolateral prefrontal cortex, localised via a neuronavigation system and a 6-month longitudinal follow-up. The primary endpoint will be the number of responders per group, defined by a decrease of at least 50% in the initial score on the Montgomery and Asberg Rating Scale (MADRS) at the end of rTMS sessions. The secondary endpoints will be: response rate 1 month after rTMS sessions; number of remissions defined by a MADRS score of <8 at the endpoint and 1 month after; the number of responses and remissions maintained over the next 6 months; quality of life; and the presence of predictive markers of the therapeutic response: clinical (dimensional scales), neuropsychological (evaluation of cognitive functions), motor (objective motor testing) and neurophysiological (cortical excitability measurements). DISCUSSION: The purpose of our study is to check the assumption of iTBS superiority in the management of unipolar depression and we will discuss its effect over time. In case of a significant increase in the number of therapeutic responses with a prolonged effect, the iTBS protocol could be considered a first-line protocol in resistant unipolar depression. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier NCT02376491 . Registered on 17 February 2015 at http://clinicaltrials.gov .

Cytomegalovirus encephalitis: Undescribed diffusion-weighted imaging characteristics. Original aspects of cases extracted from a retrospective study, and from literature review.

INTRODUCTION: There is paucity of studies analyzing DWI in MRI sequences when imaging cytomegalovirus (CMV) meningoencephalitis. The main objective of this study is to demonstrate that DWI sequence is mandatory when imaging immunocompromised patients presenting with encephalitic symptoms, as this sequence can reveal very peculiar lesions in the setting of CMV encephalitis. PATIENTS AND METHOD: Three CSF PCR CMV positive cases were identified in a 13-year retrospective study with MRI scans including T1, FLAIR, DWI with automated ADC calculation, and T1 with contrast injection, and were reviewed by a senior neuroradiologist. RESULTS: Our three cases presented multiple high-signal intensity punctiform lesions in DWI, which uniformly were in restricted diffusion. Each patient had multiple lesions (mean 19.3, range 12-30): 96.5% were supratentorial and 3.5% were infratentorial. Among supratentorial lesions, 62.5% were subependymal, 28.6% were periventricular and 8.9% were subcortical. Some lesions remained in a long lasting restricted diffusion state. All cases had FLAIR curvilinear periventricular high signal intensities. No contrast uptake was found. DISCUSSION: Punctiform DWI lesions had a clear ventricle wall tropism, consistent with classical autopsy findings. The classical histological knowledge-compatible explanation for long lasting diffusion restriction is non-lethal cytotoxic edema owing to CMV inclusions. CONCLUSION: Subependymal and periventricular punctiform restricted diffusion lesions in the setting of meningoencephalitis in immunocompromised patients seem highly evocative of CMV encephalitis. The diffusion sequence probably reveals focal lesions constitutive of cellular viral inclusions.

A phenotype of atypical apraxia of speech in a family carrying SQSTM1 mutation.

SQSTM1 mutations, coding for the p62 protein, were identified as a monogenic cause of Paget disease of bone and of amyotrophic lateral sclerosis. More recently, SQSTM1 mutations were identified in few families with frontotemporal dementia. We report a new family carrying SQSTM1 mutation and presenting with a clinical phenotype of speech apraxia or atypical behavioral disorders, associated with early visuo-contructional deficits. This study further supports the implication of SQSTM1 in frontotemporal dementia, and enlarges the phenotypic spectrum associated with SQSTM1 mutations.

Challenging the diagnosis of primary angiitis of the central nervous system: a single-center retrospective study.

OBJECTIVE: (1) To describe a series of adults assessed for suspected primary angiitis of the central nervous system (PACNS) and their final diagnosis; (2) to describe and compare presenting features of PACNS and reversible cerebral vasoconstriction syndrome (RCVS); and (3) to evaluate the specificity of the presenting features of RCVS. METHODS: Patients evaluated at our institution between 2000 and 2008 for a possible CNS vasculitis and investigated by conventional angiography and/or brain biopsy were retrospectively analyzed. The inclusion criteria were a clinicoradiological presentation and cerebral angiography and/or brain biopsy raising the hypothesis of isolated cerebral vasculitis; and absence of identifiable etiology at the time of conventional angiogram and/or brain biopsy. RESULTS: Among 58 cases evaluated, 37 met the inclusion criteria and 33 were included in the study. Thirteen patients had RCVS. Thunderclap headaches, the absence of a focal neurological deficit, a convexal subarachnoid hemorrhage and/or normal brain parenchyma on magnetic resonance imaging, and "string of beads" appearance on conventional angiography had high diagnostic value. Six patients had other noninflammatory vascular disorders (intracranial atherosclerosis, cryptogenic embolism, and genetic vasculopathy). Six patients had infection or malignancy. Eight patients were diagnosed with PACNS; their clinical presentation and disease course were heterogeneous. Brain biopsy was performed in 3 cases (positive in 1). CONCLUSION: RCVS is an important differential diagnosis of CNS vasculitis. Its particular presentation should allow rapid identification in order to avoid pointless investigations and treatment. The frequent lack of histological proof and heterogeneous presentation of PACNS illustrated the nosological uncertainties of this label.

Ischemia-modified albumin and heart fatty acid-binding protein: could early ischemic cardiac biomarkers be used in acute stroke management?

BACKGROUND: The detection of biomarkers such as ischemia-modified albumin (IMA) and heart fatty acid-binding protein (HFABP) is used in the early diagnosis of acute myocardial infarction. As these biomarkers are not organ specific, we tested them in the neurovascular field. METHODS: A total of 41 patients with acute stroke were enrolled (31 ischemic strokes and 10 intracerebral hemorrhages). IMA and HFABP levels were measured in serum samples collected within 4.5 hours of stroke onset. Clinical, imaging, and outcome data were recorded. RESULTS: No difference in baseline IMA or HFABP was found between patients with ischemic and hemorrhagic stroke. There was no correlation among biomarker levels at admission, National Institutes of Health Stroke Scale score, or stroke volume. Neither of the biomarkers could predict short-term prognosis. CONCLUSIONS: IMA and HFABP do not appear to be relevant in acute stroke management.