The Role of Treatment-Related Parameters and Brain Morphology in the Lesion Volume of Magnetic-Resonance-Guided Focused Ultrasound Thalamotomy in Patients with Tremor-Dominant Neurological Conditions.

PURPOSE: To determine the best predictor of lesion volume induced by magnetic resonance (MR)-guided focused ultrasound (MRgFUS) thalamotomy in patients with tremor-dominant symptoms in Parkinson's disease (PD) and essential tremor (ET) patients. METHODS: Thirty-six neurological patients with medication-refractory tremor (n°19 PD; n°17 ET) were treated using a commercial MRgFUS brain system (Exablate Neuro 4000, Insightec) integrated with a 1.5 T MRI unit (Sigma HDxt; GE Medical System). Linear regression analysis was used to determine how the demographic, clinical, radiological (Fazekas scale), volumetric (total GM/WM/CSF volume, cortical thickness), and MRgFUS-related parameters [Skull Density Ratio (SDR), n° of transducer elements, n° of sonications, skull area, maximal energy delivered (watt), maximal power delivered (joule), maximal sonication time delivered, maximal mean temperature reached (T°C_max), accumulated thermal dose (ATD)] impact on ventral intermediate (VIM)-thalamotomy-related 3D volumetric lesions of necrosis and edema. RESULTS: The VIM thalamotomy was clinically efficacious in improving the tremor symptoms of all the patients as measured at 1 week after treatment. Multiple regression analysis revealed that T°C_max and n° of transducer elements were the best predictors of the necrosis and edema volumes. Moreover, total WM volume also predicted the size of necrosis. CONCLUSIONS: Our study provides new insights into the clinical MRgFUS procedures that can be used to forecast brain lesion size and improve treatment outcomes.

MR-Guided Focused Ultrasound for Refractory Epilepsy: Where Are We Now?

Epilepsy is one of the most common neurological diseases in both adults and children. Despite improvements in medical care, 20 to 30% of patients are still resistant to the best medical treatment. The quality of life, neurologic morbidity, and even mortality of patients are significantly impacted by medically intractable epilepsy. Nowadays, conservative therapeutic approaches consist of increasing medication dosage, changing to a different anti-seizure drug as monotherapy, and combining different antiseizure drugs using an add-on strategy. However, such measures may not be sufficient to efficiently control seizure recurrence. Resective surgery, ablative procedures and non-resective neuromodulatory (deep-brain stimulation, vagus nerve stimulation) treatments are the available treatments for these kinds of patients. However, invasive procedures may involve lengthy inpatient stays for the patients, risks of long-term neurological impairment, general anesthesia, and other possible surgery-related complications (i.e., hemorrhage or infection). In the last few years, MR-guided focused ultrasound (MRgFUS) has been proposed as an emerging treatment for neurological diseases because of technological advancements and the goal of minimally invasive neurosurgery. By outlining the current knowledge obtained from both preclinical and clinical studies and discussing the technical opportunities of this therapy for particular epileptic phenotypes, in this perspective review, we explore the various mechanisms and potential applications (thermoablation, blood-brain barrier opening for drug delivery, neuromodulation) of high- and low-intensity ultrasound, highlighting possible novel strategies to treat drug-resistant epileptic patients who are not eligible or do not accept currently established surgical approaches. Taken together, the available studies support a possible role for lesional treatment over the anterior thalamus with high-intensity ultrasound and neuromodulation of the hippocampus via low-intensity ultrasound in refractory epilepsy. However, more studies, likely conceiving epilepsy as a network disorder and bridging together different scales and modalities, are required to make ultrasound delivery strategies meaningful, effective, and safe.

Cervical Artery Dissection and Patent Foramen Ovale in Juvenile Stroke: Causality or Casuality? A Familiar Case Report.

Cervical artery dissection (CAD) and Patent Foramen Ovale (PFO) are important causes of stroke in young patients. Although PFO is considered an independent risk factor for cerebral infarction in young adults with cryptogenic stroke, other concomitant causes may be necessary to cause brain injury. PFO could be a predisposing factor of stroke through several mechanisms including paradoxical embolism from a venous source, thrombus formation in atrial septum, or atrial arrhythmias causing cerebral thromboembolism. The pathophysiology of CAD is poorly understood and includes both constitutional and environmental factors. A causal association is often difficult to establish, as other predisposing factors may also play a role in CAD etiopathogenesis. We present a family with ischemic stroke (a father and his three daughters), in which the two different stroke causes are present. We hypothesized that a paradoxical embolism caused by PFO, associated with arterial wall disease, in the presence of a procoagulant state, could produce arterial dissection and then stroke.

Effect of MAO-B Inhibitors on Neurometabolic Profile of Patients Affected by Parkinson Disease: A Proton Magnetic Resonance Spectroscopy Study.

Parkinson's Disease (PD) is the most common neurodegenerative movement disorder whose treatment is symptomatic. No suitable methods for assessing the effects of dopaminergic drugs on disease progression in clinical trials have yet been provided. The aim of this longitudinal study is to evaluate the influence of rasagiline and selegiline on neurometabolic profile in de novo PD patients by using Proton Magnetic Resonance Spectroscopy (1H-MRS). We enrolled de novo PD patients who were divided into two groups of 20 patients each, according to the dopaminergic treatment prescribed at the baseline visit (rasagiline or selegiline). At the baseline visit and after 12 months, all patients underwent neurological evaluation as well as 1H-MRS. Forty healthy controls (HC) underwent 1H-MRS at baseline and after 12 months. PD patients, compared to HC, showed significantly lower concentrations of NAA in the motor cortex, while the Cho levels showed a decreasing trend. After 12 months of therapy, the 1H-MRS study revealed that rasagiline and selegiline in a similar way were able to restore the NAA levels to values similar to those of HC. In addition, this neurometabolic change showed a correlation with UPDRS-III scores. This is the first longitudinal study that provides preliminary evidence that 1H-MRS may be a suitable method to evaluate objectively the influence of MAO-B inhibitors on the neurometabolic profile of PD patients. These results could open a new scenario on the hypothesis of a drug-induced slowing effect of PD progression.

Neuropsychological implication in possible antibody-negative limbic encephalitis: a clinical case report.

Autoimmune limbic encephalitis is an antibody-mediated brain inflammatory process, which typically involves the medial temporal lobe. Diagnosis requires the presence of antineuronal antibodies, but sometimes patients present clinical features of limbic encephalitis despite negative serology. Thus, the diagnosis of antibody-negative limbic encephalitis is difficult to make, and it must often rely largely on exclusion of other causes. This current case report describes a 28-year-old male that presented 2 months after the acute event with radiological changes typical of limbic encephalitis, but with no identifiable antibody and neuropsychological impairment. Antibody responses to neurotropic viruses and antibody-mediated encephalitis were negative in serum and cerebrospinal fluid. Magnetic resonance imaging showed signs of hyperintensity in the hippocampus bilaterally, amygdala and left pulvinar. The neuropsychological evaluation showed a deficit in emotional face recognition and severe autobiographical amnesia. Bilateral damage to the medial temporal lobe and hippocampus, including the amygdala, is associated with alterations in autobiographical memories. The neuropsychological impairment documented in this current case expands the range of clinical features of antibody-negative encephalitis and provides evidence that the memory deficit in this disorder is more extensive than was previously recognized.

Asymptomatic lymphangioleiomyomatosis: Large cyst mimicking a hydropneumothorax in a healthy patient.

Lymphangioleiomyomatosis (LAM) is a rare, idiopathic, cystic disease that affects lungs of young women at childbearing age. Usually, LAM clinical manifestations are pneumothorax, progressive dyspnea and chylous pleural effusions. In many cases, due to unusual and nonspecific symptoms, LAM is mis-recognized and patients, who are affected by such disease, receive delayed diagnosis. This case report focuses on a 45-year-old woman patient with asymptomatic lymphangioleiomyomatosis who presented a big cyst which makes it looks like hydropneumothorax condition. Although chest radiograph and following CT scan has given an incidental diagnosis of right hydropneumothorax, treatment with drainages and video-assisted thorascopic surgery, instead, has allowed us to formulate correct diagnosis of cysts in LAM.

Anton's Syndrome associated with autotopagnosia.

We describe an unusual case of a 68-year-old male affected by cerebral amyloid angiopathy and cortical blindness associated with Anton's syndrome. In addition, our patient presented with autotopagnosia, a form of agnosia characterized by loss of body spatial representation. Neuropsychological assessment evidenced cognitive impairment. Magnetic Resonance Imaging showed hemorrhagic foci in the left occipital and right occipito-parietal lobe, paratrigonal white matter, and post-ischemic parenchymal gliosis. The pattern-reversal of visual evoked potentials were indicative bilateral visual pathway of integrity of the. After a neurological damage, patients could show a denial of their own deficit; however, the association between anosognosia and autotopagnosia represents a rare neurological condition. The simultaneous onset of unusual neuropsychological syndromes could be related to involvement of a complex brain network.

A case report on crossed aphasia in dextrals: Consideration about clinical features and neural network.

RATIONALE: The term crossed aphasia in dextrals (CAD) describes aphasia following a right hemisphere lesion in right-handed subjects. The diagnostic criteria for CAD, defined on the basis of clinical cases observed over the years, are aphasia; lesion in right hemisphere; strong preference for right hand use without familial history of left handedness; structural integrity of left hemisphere; and absence of brain damage in childhood. The studies of CAD have mainly been focused on the neurobiological mechanisms underlying the functional neurocognitive lateralization and organization of the brain, such as a dissociation between language and handedness, language and praxis, or other cognitive functions.Patient concerns: We described a case of a patient affected by an aphasic syndrome following cerebral hemorrhage located in right hemisphere. DIAGNOSIS: Considering the correlation between clinical data and instrumental investigations such as magnetic resonance imaging, we diagnose the patient with non-fluent aphasia. Specifically, the patient came to our attention showing a trans-cortical mixed aphasia that, later, developed in a trans-cortical motor aphasia. Contrary to most cases of CAD, our patient does not show apraxia and visuo-spatial neglect. Interventions language and visual attention when latter functions are related to right hemisphere. INTERVENTIONS: The rehabilitation program consisted in exercises stimulating verbal fluency, comprehension, reading, and writing. OUTCOMES: After 5 months of rehabilitation patient showed significant improvement in comprehension and absence of echolalia. LESSONS: At present there is no agreement about pathogenesis of CAD and neural mechanism is still unclear. Considering the clinical symptomatology, we can argue that we observed a non-fluent aphasia. However, a more large sample should be studied to asses the role of brain circuits.

A multidisciplinary approach to assess recovery of consciousness in a patient with moyamoya disease.

INTRODUCTION: Moyamoya disease (MMD) meaning "hazy puff of smoke" in Japanese is a rare chronic cerebrovascular syndrome characterized by progressive stenosis and occlusion of the internal carotid arteries (ICAs) anterior cerebral arteries (ACAs), and middle cerebral arteries (MCAs). METHODS: Our moyamoya patient with severely impaired cognitive and motor functions underwent a specific motor and neuropsychological rehabilitative treatments to assess the recovery of consciousness. RESULTS: Results obtained showed an improvement of clinical and neuropsychological examination. These findings highlighted the importance of an intensive rehabilitation techniques used in the care of disorders of consciousness patients. CONCLUSIONS: The use of sensory methods provides advantages for the rehabilitation. In fact, in this study, we showed a correlation between sensory stimulation and changes in patient's clinical status.

DCE and DSC perfusion MRI diagnostic accuracy in the follow-up of primary and metastatic intra-axial brain tumors treated by radiosurgery with cyberknife.

BACKGROUND: The differential diagnosis between radiation necrosis, tumor recurrence and tumor progression is crucial for the evaluation of treatment response and treatment planning. The appearance of treatment-induced tissue necrosis on conventional Magnetic Resonance Imaging (MRI) is similar to brain tumor recurrence and it could be difficult to differentiate the two entities on follow-up MRI examinations. Dynamic Susceptibility Contrast-enhanced (DSC) and Dynamic Contrast-Enhanced (DCE) are MRI perfusion techniques that use an exogenous, intravascular, non-diffusible gadolinium-based contrast agent. The aim of this study was to compare the diagnostic accuracy of DSC and DCE perfusion MRI in the differential diagnosis between radiation necrosis and tumor recurrence, in the follow-up of primary and metastatic intra-axial brain tumors after Stereotactic RadioSurgery (SRS) performed with CyberKnife. METHODS: A total of 72 enhancing lesions (57 brain metastases and 15 primary brain tumors) were analyzed with DCE and DSC, by means of MRI acquisition performed by 1,5 Tesla MR scanner. The statistical relationship between the diagnosis of tumor recurrence or radiation necrosis, decided according to clinicoradiologically criteria, rCBV and Ktrans was evaluated by the point-biserial correlation coefficient respectively. RESULTS: The statistical analysis showed a correlation between the diagnosis of radiation necrosis or recurrent tumor with Ktrans (rpb = 0.54, p < 0.001) and with rCBV (rpb = 0.37, p = 0.002). The ROC analysis of rCBV values demonstrated a good classification ability in differentiating radiation necrosis from tumour recurrence as well as the Ktrans. The optimal cut-off value for rCBV was k = 1.23 with 0.88 of sensitivity and 0.75 of specificity while for Ktrans was k = 28.76 with 0.89 of sensitivity and 0.97 of specificity. CONCLUSIONS: MRI perfusion techniques, particularly DCE, help in the differential diagnosis by tumor recurrence and radiation necrosis during the follow-up after radiosurgery.

Evaluation of US and MRI techniques for carotid stenosis: a novel phantom approach.

Carotid atherosclerosis is very important in the pathogenesis of cerebral ischemia. Ultrasonography (US) and magnetic resonance imaging (MRI) are the predominant noninvasive techniques capable to identify the presence and stage of intra-plaque hemorrage. In this work, we propose a novel dedicated phantom that can be used for both US and MRI scanners to evaluate carotid atherosclerotic lesions. The phantom consists of a polymethyl metacrylate (PMMA) diagonally crossed by a PMMA hollow cylinder simulating a blood vessel. To simulate a stenosis, we inserted a plastic hollow tube inside the cylinder. Quantitative image analysis, based on accuracy measurements, was performed on two US and two MRI scanners. The accuracy measurements have highlighted the use of the 3.0 T MRI scanner to characterize the vessel stenosis. However, no significant difference between US and MRI techniques was found in Fisher exact test and inter-rater agreement. The concordance correlation coefficient showed a moderate agreement between some methods. Agreement between 3.0 T and other methods results poor, and this could be due to the fact that the 3.0 T has a better resolution compared to a US and MR 1.5 T. These methods seem to have similar efficacies for the evaluation of vessel stenosis, legitimizing the use of the developed phantom as a versatile and reproducible instrument that could be used during quality controls programs.

The role of cognitive rehabilitation in limbic encephalitis: A case report.

RATIONALE: Limbic encephalitis is a parenchymal inflammation caused by viral, bacterial, or other microbial and postinfectious agents, which is usually expressed by multifocal neurological signs and cognitive impairment. PATIENT CONCERNS: A 50-year-old female was admitted in postacute phase, at our rehabilitative Center, to undertake neuro-motor treatment for a period of 4 months. DIAGNOSES: The patient was affected by limbic encephalitis. Clinical presentation revealed attention, memory and executive dysfunctions, as well as behavioral changes, emotional dysregulation and reduction of self-awareness. INTERVENTIONS: The patients received an intensive cognitive and motor rehabilitation training. OUTCOMES: Neuropsychological assessment and magnetic resonance imaging were performed before and after rehabilitative training to evaluate the cognitive and cerebral changes induced by treatment. The patient showed an improvement in cognitive performances and behavioral aspects. LESSONS: The reducing cognitive deficits, especially memory deficits, could improve quality of life by using available cognitive resources.

Risk factors of transient global amnesia: Three case reports.

INTRODUCTION: Transient global amnesia (TGA) is characterized by a sudden onset of anterograde and retrograde amnesia, sometimes associated with mild subclinical neuropsychological deficits and vegetative symptoms, lasting for days after the episode. Migraine history, cardiovascular risk factors, and emotional stress are considered possible risk factors. TGA usually occurs during the seventh decade of life, that is, when risk factors and concomitant pathologies have a higher incidence. CASE PRESENTATION: We report 3 cases of TGA triggered by different causes (cardiovascular risk factors, emotional stress, and orgasm) with an unusual young onset (patient 1 was a 40-year-old woman, patient 2 was a 21-year-old woman, and patient 3 a 32-year-old man). The patients underwent neuroimaging and cardiovascular examination, and neuropsychological evaluation, without important abnormalities. TGA completely recovery within 1 to 7 days. CONCLUSIONS: The occurrence of different precipitating events and accurate questioning (in the absence of head trauma) seem to be key features in making the diagnosis of TGA, besides a complete neuropsychiatric and cardiovascular assessment.

A case report of recessive myotonia congenita and early onset cognitive impairment: Is it a causal or casual link?

RATIONALE: Myotonia congenita (MC) is a non-dystrophic myotonia inherited either in dominant (Thomsen) or recessive (Becker) form. MC is due to an abnormal functioning of skeletal muscle voltage-gated chloride channel (CLCN1), but the genotype/phenotype correlation remains unclear. PATIENT CONCERNS: A 48-year-old man, from consanguineous parents, presented with a fixed muscle weakness, muscle atrophy, and a cognitive impairment. Notably, his brother presented the same mutation but with a different phenotype, mainly involving cognitive function. INTERVENTIONS: The patient was submitted to cognitive assessment, needle electromyography, brain and muscle MRI, and genetic analysis. OUTCOMES: The Milan Overall Dementia Assessment showed short-term memory, verbal fluency and verbal intelligence impairment. His genetic analysis showed a recessive splice-site mutation in the CLCN1 gene (IVS19+2T>A). Muscle MRI revealed a symmetric and bilateral fat infiltration of the tensor of fascia lata, gluteus medius, and gluteus maximus muscles, associated to mild atrophy. DIAGNOSIS: Recessive myotonia congenita was diagnosed. LESSONS: Further studies should establish if and to which extent the CLCN1 mutation is responsible for this c MC phenotype, taking into account a gene-gene and /or a gene-environment.

When dysphoria is not a primary mental state: A case report of the role of the aromatic L-aminoacid decarboxylase.

RATIONALE: The aromatic L-amino acid decarboxylase (AADC) deficiency (AADCD) is a rare, autosomal recessive neurometabolic disorder caused by a deficit of the AADC that is involved in serotonin and dopamine biosynthesis, causing as a consequence, their deficits, but also a lack of norepinephrine and epinephrine, given that dopamine is their precursor. PATIENT CONCERNS: We report the case of a Caucasian 43-year-old woman heterozygous for p.Ser250Phe in DDC, encoding for AADC with a positive family history for behavioral problems. DIAGNOSES: Since adolescence, she manifested behavioral abnormalities. Three months before the admission to our hospital, she presented with a permanent dystonic posture at the 4 limbs with numbness and tingling, diplopia, and low potassium levels. She was treated with muscle relaxants and potassium, but with no results. Olanzapine was administrated, worsening mood problems. Later, after fever, low potassium levels, and increased difficulty to move, she was admitted to the neurology unit where, after bradycardia alternating with atrial and ventricular fibrillation, she had loss of consciousness. She started to complain involuntary parossistic eye and head movements, bilateral ptosis, oculogyric crises with dystonia of the head, muscle hypotrophy, and absent deep tendon reflexes. During the hospital stay, she continued having episodes of untreatable bradycardia and fever. INTERVENTIONS: Hemocultures were performed, resulting positive for Enterococcus faecalis and Acinetobacter baumanii. Whole exome sequencing was performed evidencing that the patient harbored the heterozygous p.Ser250Phe variant in the gene DDC. OUTCOMES: A treatment with Pyridoxine and Pramipexole was prescribed, but never started because she died. LESSONS: The heterozygosity for p.Ser250Phe may have influenced the clinical manifestations, given that the patient presented some overlapping symptoms with those in AADCD, but while AADCD normally is diagnosed during childhood, the fact that the patient carried the mutation in heterozygosity may have alleviated and delayed the clinical manifestations.

Acute onset of bulbar amyotrophic lateral sclerosis after flu - look at the differential diagnosis: A case report.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting upper and lower motor neurones. It can be either familial (fALS) or sporadic (sALS). ALS is characterized by muscle weakness and atrophy that can involve the limbs and trunk (i.e. the spinal form of the disease) or speech and swallowing (i.e. the bulbar form). The aetiology of sALS remains unclear although a gene-environment interaction has been proposed as a concomitant trigger for the neurodegenerative process together with viral infections, smoking, heavy metals and pesticide exposure. Herein, we report the case of a 67-year-old woman who experienced an acute onset of bulbar ALS with an atypical clinical course that was probably triggered by a bout of influenza.

Quantitative, functional MRI and neurophysiological markers in a case of Gerstmann-Sträussler-Scheinker syndrome.

Gerstmann-Sträussler-Scheinker syndrome (GSS) is an inherited autosomal dominant prion disease, caused by a codon 102 proline to leucine substitution (P102L) in the prion protein gene (PRNP). We describe the case of a 40-year-old male, affected by a slowly progressive gait disturbance, leg weakness and cognitive impairment. Genomic DNA revealed a point mutation of PRNP at codon 102, resulting in P102L, and the diagnosis of GSS was confirmed. Somatosensory evoked potentials showed alterations of principal parameters, particularly in the right upper and lower limbs. Laser-evoked potentials were indicative of nociceptive system impairment, especially in the right upper and lower limbs. Conventional magnetic resonance imaging (MRI) revealed marked atrophy of the vermis and cerebellar hemispheres and mild atrophy of the middle cerebellar peduncles and brainstem, as confirmed by a brain volume automatic analysis. Resting-state functional MRI showed increased functional connectivity in the bilateral visual cortex, and decreased functional connectivity in the bilateral frontal pole and supramarginal and precentral gyrus. Albeit limited to a single case, this is the first study to assess structural and functional connectivity in GSS using a multimodal approach.

Functional Evaluation of Awareness in Vegetative and Minimally Conscious State.

OBJECTIVE: The aim of this study was to assess differences in brain activation in a large sample of Vegetative State (VS) and Minimally Conscious State (MCS) patients, using functional magnetic resonance imaging (fMRI). METHODS: We studied 50 patients four to seven months after brain injury. By using international clinical criteria and validated behavioural scales such as the Glasgow Coma Scale and the Clinical Unawareness Assessment Scale, the patients were grouped into VS (n=23) and MCS (n=27). All patients underwent to fMRI examination. After 6 months, the patients were reassessed using Glasgow Outcome Scale and Revised Coma Recovery Scale. RESULTS: fMRI showed significant (p<0.01, cluster-corrected) brain activation in the primary auditory cortex bilaterally during the acoustic stimuli in patients with both VS and MCS. However, ten patients clinically classified as VS, showed a pattern of brain activation very similar to that of MCS patients. Six months later, these ten VS patients had significant clinical improvement, evolving into MCS, whereas the other VS patients and patients with MCS remained clinically stable. CONCLUSION: Brain activity could help in discerning whether the status of wakefulness in VS is also accompanied by partial awareness, as occurs in MCS. This may have very important prognostic implications.