Francesco Cavallieri

MRI Correlates of Parkinson’s Disease Progression: A Voxel Based Morphometry Study

We investigated structural brain differences between a group of early-mild PD patients at different phases of the disease and healthy subjects using voxel-based morphometry (VBM). 20 mild PD patients compared to 15 healthy at baseline and after 2 years of follow-up. VBM is a fully automated technique, which allows the identification of regional differences in the gray matter enabling an objective analysis of the whole brain between groups of subjects. With respect to controls, PD patients exhibited decreased GM volumes in right putamen and right parietal cortex. After 2 years of disease, the same patients confirmed GM loss in the putamen and parietal cortex; a significant difference was also observed in the area of pedunculopontine nucleus (PPN) and in the mesencephalic locomotor region (MLR). PD is associated with brain morphological changes in cortical and subcortical structures. The first regions to be affected in PD seem to be the parietal cortex and the putamen. A third structure that undergoes atrophy is the part of the inferior-posterior midbrain, attributable to the PPN and MLR. Our findings provide new insight into the brain involvement in PD and could contribute to a better understanding of the sequence of events occurring in these patients.

Subacute copper-deficiency myelopathy in a patient with occult celiac disease.

Context: Acquired copper deficiency represents a rare cause of progressive myelopathy presenting with sensory ataxia and spastic gait. The time interval from neurological symptoms onset to diagnosis of myelopathy ranges from 2 months to several years in almost all cases, mimicking the clinical course of subacute combined degeneration due to vitamin B12 deficiency. Findings: A 60-year-old man, without any gastrointestinal symptoms, developed over the course of one week rapidly progressive gait imbalance, tingling and numbness in his feet and ascending lower limb weakness. Spine magnetic resonance imaging revealed hyperintensity involving cervical and dorsal posterior columns of spinal cord. Blood analysis revealed undetectable serum copper levels, low serum ceruloplasmin and positive serum Immunoglobulin A anti-tissue transglutaminase. Upper gastrointestinal endoscopy was performed revealing duodenal villous atrophy consistent with a malabsorption pattern. A gluten-free diet in association with intravenous then oral copper supplementation prompted sustained normalization of serum copper levels and progressive clinical improvement. Conclusion/Clinical Relevance: We report a rare case of myelopathy induced by copper deficiency secondary to undiagnosed celiac disease, peculiarly presenting with a subacute onset. This case expands the neurological presentation and clinical course of myelopathy due to acquired copper deficiency. We suggest investigation of copper deficiency in patients presenting with subacute or even acute sensory ataxia and spastic gait. Detection of hypocupremia in patients without a previous history of gastric surgery should lead to diagnostic testing for celiac disease even in the absence of any obvious gastrointestinal symptoms.

The wide spectrum of cerebrotendinous xanthomatosis: Case report of a rare but treatable disease

Cerebrotendinous xanthomatosis (CTX) is an autosomal-recessive disorder of lipid storage caused by mutations in the CYP27A1 gene, coding for a sterol 27-hydroxylase, leading to increased deposition of cholesterol in multiple tissues. CTX is characterized by the association of early non-neurological manifestations and adult-onset neurological dysfunctions (spastic ataxia, dementia, psychiatric disorders, peripheral neuropathy). Early and long-term treatment with chenodeoxycholic acid (CDCA) can slow down neurological symptoms progression, but diagnosis usually has a delay of several years. We report two Italian siblings having quite different phenotypes associated to a G-to-A transition in the c-1263 terminal causing a splicing alteration. This mutation has not been described before in Italy, and has been reported once in Japan. This case widens the clinical and genetic spectrum of Cerebrotendinous Xantomatosis in Italy and would like to suggest the importance of genetic testing in patients with autosomal recessive spastic paraparesis associated with typical non-neurological symptoms.

Pearls & Oy-sters: Rapidly progressive dementia Prions or immunomediated?

Voltage-gated potassium channel (VGKC) antibody–associated encephalitis is a well-known form of limbic encephalitis characterized by acute to subacute onset of confusion and cognitive impairment, mediotemporal seizures, and psychiatric disturbances.

Central pontine myelinolysis and poorly controlled diabetes: MRI’s hints for pathogenesis

Dear Sir, Central pontine myelinolysis (CPM) is usually associatedwith a rapid correction of hyponatremia [1, 2]. In a patient with chronic hyponatremia, oligodendrocytes in the pons decrease their inner osmolarity to protect them from swelling. Thereafter, any rapid osmotic shift in the opposite direction caused by the hypertonic fluid can induce the swollen cells to shrink, leading to osmotic demyelination [1, 2]. Typical MRI features in CPM are characterized by cytotoxic edema (DWI hyperintensity and ADC hypointensity) consistent with shrinkage of the pontine cells [3]. We describe a case of CPM due to poorly controlled diabetes with brain MRI features compatible with vasogenic edema (DWI and ADC hyperintensity) that may suggest an extracellular space expansion rather than shrinkage of the pontine cells [4]. A 27-year-old man with poorly controlled type 1 diabetes mellitus presented with right leg weakness since 3 days. He had been diagnosed with type 1 diabetes mellitus when he was 19 years old. His therapy adherence was erratic with repeated episodes of diabetic ketoacidosis and hypoglycemic coma. There was no history of alcohol abuse. He was polyuric and he had been vomiting for 1 hour. Neurological examination at admission revealed mild paresis in his right lower limb, bilateral intention tremor at the heel/ankle test and ataxic gait. Blood tests at admission were consistent with poorly controlled diabetes, showing high levels of serum glucose (9.22 mmol/L) and of glycated hemoglobin (hemoglobin A1c 119 mmol/mol); serum electrolytes were within the normal ranges. Brain MRI (Fig. 1) demonstrated a hyperintense region in FLAIR and T2-weighted images in the central portion of the rostral pons with a bilaterally symmetric pattern consistent with CPM. Axial diffusion-weighted magnetic imaging (DWI) and axial apparent diffusion coefficient (ADC) map revealed the same hyperintense signal abnormalities. These f indings were consis tent with vasogenic edema. Hyperglycemia was adjusted over 24 h with no change in serum electrolyte concentration. During 2 weeks of hospital stay, his blood glucose fluctuated widely with severe hyperand hypoglycemia at preprandial measurements (from 2.20 to 32.78 mmol/L); therefore, the patient underwent implantation of a subcutaneous insulin pump. Brain MRI performed 2 and 4 months after the discharge showed the persistence of the hyperintense alterations in FLAIR and T2-weighted images with the disappearance of the hyperintense signal abnormalities seen in the axial DWI sequences (Fig. 2). It is unusual for CMP to develop in the absence of significant changes in the serum sodium concentration. On the one hand, CMP is usually associated with a rapid correction of severe hyponatremia which typically occurs in malnourished or alcoholic patients, after prolonged use of diuretic drugs, after liver transplantation, and also in the setting of lymphoma and leukemia [1, 2, 5, 6]. In a previous case series, hypernatremia, hyperglycemia, and hyperazotemia, alone or combined, accounted for the hyperosmolality which is supposed to drive the pathogenesis of CPM [2, 7]. On the other hand, an acute onset of a low * Antonio Fasano antonio.fasano89@gmail.com

Acute hemichorea as unusual first multiple sclerosis presentation

Patient 1 was a 39-year-old woman with an unremarkable medical history who developed acute involuntary right arm and leg movements. Neurologic examination revealed moderate dysarthria and subcontinuous, choreic movements in her right limbs, prevailing in the arm, which worsened during postural tasks. She occasionally had ballistic movements in her right limbs and abnormal dystonic postures. Continuous peribuccal and tongue involuntary movements were noted. Moreover, bilateral upper limb ataxia, gait and trunk ataxia, and brisk right tendon reflexes were found. There was no strength or sensory loss (video 1 at [Neurology.org/cp][1]). Brain MRI revealed a tumefactive, T2/fluid-attenuated inversion recovery (FLAIR) hyperintense, T1 hypointense contrast-enhancing demyelinating lesion in the left cerebral peduncle, extending to the substantia nigra and subthalamic nucleus (STN) (figure, A–C). Multiple hyperintense T2/FLAIR, T1 hypointense, non-contrast-enhancing demyelinating lesions in the hemispheric and periventricular deep white matter, brainstem, and cerebellar hemispheres were also found. All serologic tests were within normal limits. Isoelectric focusing (IEF) revealed 9 CSF oligoclonal bands (OCBs). A diagnosis of multiple sclerosis (MS) was made and the patient was treated with high-dose methylprednisolone with improvement of symptoms. [1]: http://cp.neurology.org/lookup/doi/10.1212/CPJ.0000000000000279

Post-infectious sensory neuropathy with anti-GT1a and GQ1b antibodies associated with cold urticaria

A 64 years-old woman presented subacute onset distal paraesthesia concurrently with cold-induced urticaria, a rare form of physical urticaria. Both the disturbances developed a fortnight after an upper respiratory tract infection. EMG confirmed an exclusively sensory polyneuropathy, with prolongation of distal latencies and reduction of amplitudes. Anti-GQ1b and anti-GT1a antigangliosides antibodies were found in serum. The clinical workout included CSF analysis, cryoglobulin and paraprotein search, neurotropic infective agents, neoplastic markers and extensive autoimmune disease antibodies analysis, all of which resulted negative. Intravenous immunoglobulins were administered, leading to progressive resolution of the sensory disturbance, while a combination of steroid and anti-histaminics treatment was used for the urticaria. The positivity for anti-ganglioside search with an EMG pattern characterized by a mixture of demyelinating and axonal features may suggest a nodo-paranodopathy at early stages. This is the first case of an association between an acute sensory neuropathy and cold urticaria, two immune mediated conditions apparently due to very different hypersensitivity pathways. A proposed mechanism for the co-occurence of these two conditions is presented, whereas this case expands the clinical spectrum of autoimmune diseases associated with anti-GQ1b and anti-GT1a antibodies.

Usefulness of Thromboelastography in the Detection and Management of Tissue Plasminogen Activator-Associated Hyperfibrinolysis

Rotation thromboelastometry is a viscoelastometric method that provides a rapid assessment of a patients hemostatic processes in emergency settings, allowing prompt identification of specific coagulation abnormalities. Its results thus might guide targeted replacement therapy in hemorrhagic conditions, in case of platelet or coagulation factor deficiency, or hyperfibrinolysis, which is difficult to identify otherwise. Although currently used in emergency and traumatic surgery, there are limited data about thromboelastometry in ischemic stroke, particularly in monitoring the coagulative response to recombinant tissue plasminogen activator after intravenous thrombolysis (IVT). Here we report a case of ischemic stroke complicated by a remote asymptomatic intracranial hemorrhage after IVT and additional endovascular therapy that has been successfully treated with intravenous infusion of tranexamic acid after the detection of the status of hyperfibrinolysis provided by thromboelastometry. Further studies are needed to provide the potential usefulness of thromboelastometry and tranexamic acid in ischemic stroke complicated by intracranial bleeding.

Cortical action myoclonus due to cortical laminar necrosis.

Dear Editor, Cortical myoclonus is the most common form of myoclonus, mainly affecting distal upper limbs and typically occurring during voluntary action [1]; in particular, focal cortical myoclonus is frequently caused by a focal lesion affecting excitability of the sensorimotor cortex [1]. Transcranial magnetic stimulation (TMS) evaluates the excitability state of the primary motor cortex [2], representing an important tool to study focal cortical myoclonus [3]. Cortical laminar necrosis (CLN) is defined as hyperintense cortical lesion on Magnetic Resonance Imaging (MRI) T1-weighted sequences involving specific cortical laminae observed after a subacute or chronic brain damage [4]. We here present a patient with cortical action myoclonus associated with CLN. A 61-year-old woman had a 7-year history of tremorlike involuntary jerks of the right arm during antigravity postures and voluntary movement. The tremor disappeared spontaneously at rest and during sleep. It started subacutely and presented a very slow progression overtime. On neurological examination the postural and action jerky movements appeared repetitive and pseudo-rhythmic, mainly affecting the proximal right upper limb, without any other neurological sign. Six months before the disturbance appearance, she developed central retinal vein thrombosis in the right eye relapsed 1 year later in the left eye. Treatment with Atenolol, Gabapentin, Amantadine, Levetiracetam and Clonazepam did not improve symptoms. Laboratory tests including blood cell count with acanthocytes search, serum electrolytes, thyroid function, ceruloplasmin and copper levels were normal. 3 T brain MRI disclosed a layer of increased signal in left frontoparietal cortex in correspondence of the central sulcus in Sagittal T1-weighted images (Fig. 1a). This hyperintense band was associated with hypointensity of the underlying subcortical white matter that appeared as a patchy subcortical hyperintensity area in Fluid-attenuated inversion recovery (FLAIR) sequences (Fig. 1b). T2-weighted images showed corresponding hyperintense regions on T1 and FLAIR sequences, as subtly cortical hypointense areas with hyperintense signal of the underlying subcortical white matter (Fig. 1c, d). Diffusion-weighted imaging (DWI) MRI revealed a layer of hyperintense signal involving the cortical grey matter of left fronto-parietal cortex (Fig. 1e), without any pathological enhancement in gadoliniumenhanced T1-weighted sequences. These findings were considered consistent with CLN. Surface electromyography (EMG) recording showed the presence of middle frequency (7–8 Hz) arrhythmic myoclonic jerks of the right arm with a mainly synchronous activation pattern of flexor F. Cavallieri (&) V. Fioravanti S. Contardi L. Codeluppi F. Valzania Department of Neuroscience, University of Modena and Reggio Emilia, S. Agostino-Estense Hospital, Via Pietro Giardini n. 1355, 41126 Modena, Italy e-mail: cava_87@hotmail.it