Daniela Marino

Altered cortical and subcortical local coherence in obstructive sleep apnea: a functional magnetic resonance imaging study

Obstructive sleep apnea (OSA) syndrome is the most common sleep‐related breathing disorder, characterized by excessive snoring and repetitive apneas and arousals, which leads to fragmented sleep and, most importantly, to intermittent nocturnal hypoxaemia during apneas. Considering previous studies about morphovolumetric alterations in sleep apnea, in this study we aimed to investigate for the first time the functional connectivity profile of OSA patients and age–gender–matched healthy controls, using resting‐state functional magnetic resonance imaging (fMRI). Twenty severe OSA patients (mean age 43.2 ± 8 years; mean apnea–hypopnea index, 36.3 h−1) and 20 non‐apneic age–gender–body mass index (BMI)‐matched controls underwent fMRI and polysomnographic (PSG) registration, as well as mood and sleepiness evaluation. Cerebro‐cerebellar regional homogeneity (ReHo) values were calculated from fMRI acquisition, in order to identify pathology‐related alterations in the local coherence of low‐frequency signal (<0.1 Hz). Multivariate pattern classification was also performed using ReHo values as features. We found a significant pattern of cortical and subcortical abnormal local connectivity in OSA patients, suggesting an overall rearrangement of hemispheric connectivity balance, with a decrease of local coherence observed in right temporal, parietal and frontal lobe regions. Moreover, an increase in bilateral thalamic and somatosensory/motor cortices coherence have been found, a finding due possibly to an aberrant adaptation to incomplete sleep–wake transitions during nocturnal apneic episodes, induced by repetitive choke sensation and physical efforts attempting to restore breathing. Different hemispheric roles into sleep processes and a possible thalamus key role in OSA neurophysiopathology are intriguing issues that future studies should attempt to clarify.

Evidence of diffuse damage in frontal and occipital cortex in the brain of patients with post-traumatic stress disorder

A number of MRI studies have shown focal or diffuse cortical gray matter (GM) abnormalities in patients with post-traumatic stress disorder (PTSD). However, the results of these studies are unclear regarding the cortical regions involved in this condition, perhaps due to the heterogeneity of the PTSD population included or to the differences in the methodology used for the quantification of the brain structures. In this study, we assessed differences in cortical GM volumes between a selected group of 25 drug-naive PTSD patients with history of adulthood trauma and 25 matched non-traumatized controls. Analyses were performed by using two different automated methods: the structural image evaluation using normalization of atrophy (SIENAX) and the voxel-based morphometry (VBM), as we trusted that if these complementary techniques provided similar results, it would increase the confidence in the validity of the assessment. Results of SIENAX and VBM analyses similarly showed that cortical GM volume decreases in PTSD patients when compared to healthy controls, particularly in the frontal and occipital lobes. These decreases seem to correlate with clinical measures. Our findings suggest that in drug-naïve PTSD patients with a history of adulthood trauma, brain structural damage is diffuse, with a particular prevalence for the frontal and occipital lobes, and is clinically relevant.

Multimodal responses induced by cortical stimulation of the parietal lobe: a stereo-electroencephalography study

The functional complexity of the parietal lobe still represents a challenge for neurophysiological and functional neuroimaging studies. While the somatosensory functions of the anterior parietal cortex are well established, the posterior parietal cortex has a relevant role in processing the sensory information, including visuo-spatial perception, visual attention, visuo-motor transformations and other complex and not completely understood functions. We retrospectively analysed all the clinical manifestations induced by intracerebral bipolar electrical stimulation in 172 patients suffering from drug-resistant focal epilepsy (mean age 25.6, standard deviation 11.6; 44% females and 56% males) with at least one electrode stereotactically implanted in the parietal cortex. A total of 1186 electrical stimulations were included in the analysis, of which 88 were subsequently excluded because of eliciting pathological electric activity or inducing ictal symptomatology. In the dominant parietal lobe, clinical responses were observed for 56 (25%) of the low-frequency stimulations and for 76 (50%) of the high-frequency stimulations. In the non-dominant parietal lobe, 111 (27%) low-frequency and 176 (55%) high-frequency stimulations were associated with a clinical response. Body scheme alteration was the only clinical effect showing a lateralization, as they were evoked only in the non-dominant hemisphere. The occurrence of somatosensory sensations, motor symptoms, dysarthria and multimodal responses were significantly associated with stimulation of the postcentral gyrus (odds ratio: 5.83, P < 0.001; odds ratio: 8.77, P < 0.001; odds ratio: 5.44, P = 0.011; odds ratio: 8.33, P = 0.006; respectively). Stimulation of the intraparietal sulcus was associated with the occurrence of sensory illusions or hallucinations (odds ratio: 8.68, P < 0.001) and eyeball/eyelid movements or sensations (odds ratio: 4.35, P = 0.047). To our knowledge, this is the only currently available complete revision of electrical stimulation of the entire parietal cortex with the aim to evaluate the neurophysiology of this relevant brain region. Our analysis offers a general overview of the multiple roles of the parietal cortex and supports its crucial involvement in different networks related to complex integrative functions.media-1vid110.1093/brain/awv187_video_abstractawv187_video_abstract.

Tarlov cysts: Clinical evaluation of an italian cohort of patients

Tarlov cyst syndrome is a rare, often asymptomatic disorder, characterised by isolated or multiple nerve-root cysts, usually occurring in the sacral spine, near the dorsal root ganglion, between the perineurium and endoneurium. The cysts may cause lower back pain, sacral radiculopathy, dyspareunia and urinary incontinence. There is little data in the literature on the relationship between Tarlov cysts and symptoms. Here, we report further details on the clinical impact of Tarlov cysts and investigate their pathogenesis and role as a cause of lumbosacral symptoms. We examined 157 patients with MRI evidence of symptomatic Tarlov cysts. Patients underwent complete neurological examination and were scored by the Hamilton Depression Rating Scale and the Visual Analogue Scale. Complete lower limb electromyography was performed in 32 patients. Clinical picture was correlated with size and number of cysts detected by MRI. Family history was recorded for signs of genetic inheritance. Almost all patients suffered perineal or lower back pain; 34 complained of sphincter and 46 of sexual disorders. Hamilton scores were abnormal, and family history was positive in a few cases. The scanty literature on Tarlov cysts mainly regards therapy by a neurosurgical approach. Our results provide new data on clinical impact and possible pathogenetic mechanisms.

Fulminant intravascular lymphomatosis mimicking acute haemorrhagic leukoencephalopathy

BACKGROUND Intravascular lymphomatosis (IVL) is a rare non-Hodgkins lymphoma, usually of B cell lineage, characterized by massive angiotropic growth. The clinical presentation of IVL may include changes in mental status, non-localizing neurological deficits, seizures, fever of unknown origin and skin changes. Because of its rarity and the absence of specific diagnostic procedures except for cerebral biopsy, diagnosis is often postmortem. Brain MRI usually shows non-specific abnormalities. The purpose of this case report is to increase the knowledge of clinical and neuroimaging features of IVL by describing the findings observed in a 71-year-old patient. CASE REPORT A 71-year-old male was admitted for right hemiparesis, acute cognitive impairment and febricula. A bone marrow biopsy resulted normal. He then developed a rapid progressive impairment of his mental status and left hemisoma motor seizures. Brain CT and MRI were interpreted as consistent with acute haemorrhagic leukoencephalopathy (AHLE), including multiple areas of restricted diffusion without gadolinium enhancement and a small focal area of gadolinium enhancement in the left temporal lobe white matter. The patient died within a few days and the autopsy led to the diagnosis of IVL. CONCLUSION IVL may present with a variety of clinical signs and symptoms, including stroke and hemiparesis. IVL may mimic AHLE at brain MRI. However, the evidence of multiple areas of restricted diffusion without gadolinium enhancement and of a small area of gadolinium enhancement could have led to the correct diagnosis. IVL should be added to the differential diagnosis of AHLE at brain MRI.

Transient periodic lateralised epileptiform discharges (PLEDs) following internal carotid artery stenting

BackgroundPeriodic lateralised epileptiform discharges (PLEDs) are EEG patterns consisting of periodic or pseudoperiodic unilateral, focal or hemispheric epileptiform discharges at a rate of 1–2 Hz. PLEDs may be triggered by acute brain injuries or systemic metabolic changes such as fever, hyperglycaemia or electrolyte imbalance and may result in disturbance of consciousness and/or neurological deficits.Case reportA 58-year-old female with a history of focal epilepsy and deep brain haematoma presented with acute change in awareness, associated with EEG evidence of PLEDs, three days after a left internal carotid artery stenting procedure. Clinical examination, laboratory testing and MRI were unchanged with respect to pre-stenting investigations.ConclusionIn this patient, PLEDs may have been triggered by local haemodynamic changes due to reperfusion after stenting in a previously damaged brain area.

Reply: The dorsal cingulate cortex as a critical gateway in the network supporting conscious awareness

Sir, We thank Herbet et al. for their interest in our recent article on the results of cortical stimulation of the parietal cortex. In their letter they highlight the importance of the cortical mapping of the medial posterior parietal cortex, including the posterior cingulum and the precuneus, and add their anecdotal findings in a small group of patients. We want to use this opportunity to spell out some relevant details in our own work, to relate our findings to Herbet et al. ’s (2014) observations, and make a few comments on their interpretation of our and their observations. The areas in question are in a functionally strategic position, connecting anterior and posterior brain regions, left and right hemispheres, and limbic and neocortical structures. In summary, in our work, among the 419 cortical stimulations associated with a clinical response, 50 were evoked in the posterior cingulum, and 62 in the precuneus. The prevalent clinical responses were somatosensory sensations (16/50, 32%) and motor symptoms (10/50, 20%) in the posterior cingulum, and visual illusions/hallucinations (18/62, 29%), eyeball/eyelid movements or sensations (9/62, 15%) and vertigo (7/62, 11%) in the precuneus. Herbet et al. pointed out that there were also rare complex subjective responses that we classified as ‘psychic phenomena’. The following synthesize and complete the description of our findings relevant to this discussion: …

Myotonic dystrophy type 2 and autoimmune chronic gastritis: an incidental association?

Myotonic dystrophy type 2 (DM2) is an autosomal dominant multisystem disease caused by a large expansion of a CCTG repeat located in intron 1 of the zinc finger protein 9 (ZNF9) gene on the chromosome 3q21.3. The clinical picture of DM2 shows similarities to as well as differences from myotonic dystrophy type 1 (DM1). DM2 is mainly characterized by myotonia, muscle dysfunction including weakness, myalgia and stiffness, cataracts, cardiac arrhythmia and endocrine disturbances [1]. A recent study found a significantly higher frequency of autoimmune disease and autoantibodies in DM2 patients compared with DM1 subjects and the general population, suggesting a strong association between DM2 and autoimmunity [2]. A 48-year-old Italian woman was recently referred to us with a 4 year history of fluctuating muscle weakness, pain and stiffness of lower limbs. Her past history revealed chronic immune thrombocytopenia (ITP), Hashimoto’s thyroiditis (HT) and mammary cancer. Family history disclosed cardiopathy, myalgias and stiffness in the paternal members. No history of autoimmune disorders was referred in the family members. On admission, neurological examination showed grip myotonia, slight weakness (MRC grade 4) of neck flexors and proximal lower limbs muscles. Routine blood analysis confirmed thrombocytopenia and uncovered mild hyperCKemia (265 U/L; normal 10–170 U/L). Electromyography showed myotonic discharges in both the proximal and distal muscles of the upper and lower limbs. Ophthalmological evaluation revealed initial cataracts. Electrocardiographic and echocardiographic examination excluded conduction abnormalities and cardiomyopathy, respectively. Molecular analysis of dystrophia myotonica protein kinase (DMPK) gene did not reveal CTG repeat expansion. Muscle biopsy (vastus lateralis) showed fiber size variability, increased internal nuclei, frequent nuclear clumps and the evidence of type 2 fiber atrophy. Fluorescence in situ hybridization using (CAGG)5 probe was performed on skeletal muscle sections: the presence of nuclear accumulation of CCUG-containing RNA confirmed the clinical diagnosis of DM2. Serum autoantibody assessment showed the elevated levels of anti-thyroglobulin and antithyroperoxidase antibodies and uncovered high titers of antiparietal cell antibodies (82.8 U/mL; normal \10 U/mL). Thus, we performed esophagogastroduodenoscopy and gastric biopsies which revealed chronic gastritis with intestinal metaplasia, mild gastric atrophy and foveolar hyperplasia, primarily affecting the body/fundus of the stomach. Moreover, further biochemical analysis showed hypergastrinemia (345 pg/mL; normal \108 pg/mL) and vitamin B12 deficiency (103 pg/mL; normal 140–900 pg/mL). However, both anemia and gastrointestinal symptoms were absent. On the basis of laboratory and histopathological findings, a diagnosis of subclinical autoimmune chronic gastritis (ACG) was established. Our case report expands the spectrum of autoimmune disorders in DM2 and further suggests a strong association F. Sicurelli (&) A. Mignarri A. Carluccio D. Marino A. Federico M. T. Dotti Neurology and Neurometabolic Unit, Department of Neurological, Neurosurgical and Behavioural Sciences, University of Siena, Viale Bracci 2, 53100 Siena, Italy e-mail: francesco.sicurelli@gmail.com

Patient-specific seizure prediction based on heart rate variability and recurrence quantification analysis

Epilepsy is often associated with modifications in autonomic nervous system, which usually precede the onset of seizures of several minutes. Thus, there is a great interest in identifying these modifications enough time in advance to prevent a dangerous effect and to intervene. In addition, these changes can be a risk factor for epileptic patients and can increase the possibility of death. Notably autonomic changes associated to seizures are highly depended of seizure type, localization and lateralization. The aim of this study was to develop a patient-specific approach to predict seizures using electrocardiogram (ECG) features. Specifically, from the RR series, both time and frequency variables and features obtained by the recurrence quantification analysis were used. The algorithm was applied in a dataset of 15 patients with 38 different types of seizures. A feature selection step, was used to identify those features that were more significant in discriminating preictal and interictal phases. A preictal interval of 15 minutes was selected. A support vector machine (SVM) classifier was then built to classify preictal and interictal phases. First, a classifier was set up to classify preictal and interictal segments of each patient and an average sensibility of 89.06% was obtained, with a number of false positive per hour (FP/h) of 0.41. Then, in those patients who had at least 3 seizures, a double-cross-validation approach was used to predict unseen seizures on the basis of a training on previous ones. The results were quite variable according to seizure type, achieving the best performance in patients with more stereotypical seizure. The results of the proposed approach show that it is feasible to predict seizure in advance, considering patient-specific, and possible seizure specific, characteristics.

A Machine Learning Approach for Epileptic Seizure Prediction and Early Intervention

Epilepsy is often associated with modifications in autonomic nervous system, which usually precede the onset of seizures of several minutes. Identifying those changes is pivotal to predict the onset of seizure and to set up an early intervention. The aim of this study was to develop a patient-specific approach to predict seizures using electrocardiogram. Time- and frequency- domain features as well as recurrence quantification analysis variables, were extracted from the RR series. A machine learning approach based on support vector machine was then applied to predict seizures. The dataset consisted of 12 patients with 38 different types of seizures. An average sensibility of 83.8% and specificity of 72.8% were obtained. The results of the proposed approach show that it is feasible to predict seizure in advance, considering patient-specific, and possibly seizure-specific, characteristics.