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.

Music Therapy in Global Aphasia: A Case Report.

Patients affected by global aphasia are no longer able to understand, produce, name objects, write and read. It occurs as a result of functional damage of ischemic or hemorrhagic origin affecting the entire peri-silvan region and frontal operculum. Rehabilitation training aims to promote an early intervention in the acute phase. We described a case of a 57-year-old female patient with left intraparenchymal fronto-temporo-parietal cerebral hemorrhage and right hemiplegia. After admission to clinical rehabilitative center, the patient was not able to perform simple orders and she presented a severe impairment of auditory and written comprehension. Eloquence was characterized by stereotypical emission of monosyllabic sounds and showed compromised praxis-constructive abilities. Rehabilitation included a program of Neurologic Music Therapy (NMT), specifically Symbolic Communication Training Through Music (SYCOM) and Musical Speech Stimulation (MUSTIM). Rehabilitative treatment was measured by improved cognitive and language performance of the patient from T0 to T1. Music rehabilitative interventions and continuous speech therapy improve visual attention and communicative intentionality. In order to confirm the effectiveness of data presented, further extensive studies of the sample would be necessary, to assess the real role of music therapy in post-stroke global aphasia.

Neuropsychological Disability in the Case of Natalizumab-Related Progressive Multifocal Leukoencephalopathy.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a viral disease characterized by progressive damage or inflammation of the cerebral white matter that can be encountered in patients with multiple sclerosis (MS). There are cases of PML caused by pharmacological agents including natalizumab. Therefore, in patients treated with this drug, early identification of PML allows changes in the treatment plan, reducing the risks of morbidity and mortality. CASE PRESENTATION: We reported the case of a 57-year-old female diagnosed with relapsing-remitting MS, who presented with PML related to natalizumab. The patient presented with change in behavioral, radiological abnormalities in the left parieto-temporal lobes. We described the longitudinal course of PML, from the diagnosis until the patient's death, documenting the progressive deterioration of her cognitive functioning, supported by changes on sequential brain scans and neurophysiological data. CONCLUSION: The neuropsychological impairment documented in this case study expands the range of treatment-related complications associated with natalizumab, and provides evidence that occurrence of "atypical" cognitive deficits in MS may support the early diagnosis of PML.

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.

Recovery of Severe Aphasia After Cranioplasty: Considerations on a Case Study.

Cranioplasty is the main surgical intervention for repairing cranial defects performed in about 80% of the patients following cancer surgery or decompressive craniectomy. Although some works have shown recovery of motor and cognitive function, including memory, attention, and executive functions, until today no studies have focused on language recovery after cranioplasty. A 68-year-old woman came to the Neurorehabilitation Unit of the IRCCS Neurolesi (Messina, Italy) because of a fluent aphasia due to a severe left nucleocapsular hemorrhage and greatly improved her motor and neuropsychological status after cranioplasty. Results confirmed that cranioplasty might significantly improve motor and neuropsychological function, besides aphasia. Healthcare professionals involved in rehabilitation should be aware of the potential role of cranioplasty in improving rehabilitative outcomes to better plan a more personalized rehabilitative program. Moreover, rehabilitation nurses can play a pivotal role within the rehabilitation process, as they are educated to interact and communicate with the patient suffering from aphasia.

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.

Agenesis of corpus callosum and frontotemporal dementia: a casual finding?

Agenesis of corpus callosum (AgCC) is a congenital malformation characterized by total or partial absence of corpus callosum with a good neuropsychological profile. Frontotemporal dementia (FTD) is the third most common cause of cortical dementia, and it is characterized by alterations in personality and social relationship, often associated with deficits in attention, abstraction, planning, and problem solving. Herein, we report a case of a 73-year-old woman presenting with FTD associated with primary AgCC. The possible "causal or casual" relationship between these 2 different conditions should be investigated in large prospective studies.

Three-dimensional volume rendering of the ankle based on magnetic resonance images enables the generation of images comparable to real anatomy.

We have applied high-quality medical imaging techniques to study the structure of the human ankle. Direct volume rendering, using specific algorithms, transforms conventional two-dimensional (2D) magnetic resonance image (MRI) series into 3D volume datasets. This tool allows high-definition visualization of single or multiple structures for diagnostic, research, and teaching purposes. No other image reformatting technique so accurately highlights each anatomic relationship and preserves soft tissue definition. Here, we used this method to study the structure of the human ankle to analyze tendon-bone-muscle relationships. We compared ankle MRI and computerized tomography (CT) images from 17 healthy volunteers, aged 18-30 years (mean 23 years). An additional subject had a partial rupture of the Achilles tendon. The MRI images demonstrated superiority in overall quality of detail compared to the CT images. The MRI series accurately rendered soft tissue and bone in simultaneous image acquisition, whereas CT required several window-reformatting algorithms, with loss of image data quality. We obtained high-quality digital images of the human ankle that were sufficiently accurate for surgical and clinical intervention planning, as well as for teaching human anatomy. Our approach demonstrates that complex anatomical structures such as the ankle, which is rich in articular facets and ligaments, can be easily studied non-invasively using MRI data.

Charles Bonnet syndrome.

Charles Bonnet syndrome (CBS) is a disorder of visual hallucinations typically occurring in older patients with visual impairment or deafferentation of the visual cortex. In this paper, which reviews the relevant literature, the aetiologies, pathophysiology, and treatment of CBS are discussed. It is suggested that the ageing of the population, associated with an increased occurrence of vision and cerebral disorders, is leading to an increase in the incidence of CBS.

Hallucinations after abrupt withdrawal of oral and intrathecal baclofen.

Since 1977 several cases of hallucinations after abrupt withdrawal of oral baclofen have been described. There are no reports of hallucinations after gradual withdrawal of oral baclofen. No one has ever described visual hallucinations after abrupt interruption of intrathecal baclofen therapy. We describe five personally observed cases of visual hallucinations occurring after sudden interruption of baclofen (in two of these cases, intrathecal baclofen) therapy. The patients were immediately submitted to routine EEG, visual evoked potentials and standard brain magnetic resonance imaging (MRI). A few days later they also underwent polysomnography, fundus oculi examination and brain MRI of the temporal lobe. All these examinations were normal. We hypothesise that these symptoms could be due to biochemical and molecular changes, chiefly in glutamatergic n-methyl-d-aspartate, GABA-A, and GABA-B receptor response, leading to increased excitability and spontaneous activity as a result of chronic use of baclofen.