Marianna Riolo

Mercaptopurine Treatment in an Adult Man with Orbital and Intracranial Rosai-Dorfman Disease.

Background. Rosai-Dorfmann disease (RDD) is a rare, idiopathic non-Langerhans cell histiocytosis, affecting children and young adults, that commonly presents as painless, massive cervical lymphadenopathy with fever, weight loss, and polyclonal hypergammaglobulinemia. Cervical lymphadenopathy and extranodal involvement are the main presentations. On the contrary, ophthalmic involvement and localisation in the central nervous system are rare. Case Report. An old man was admitted to our hospital for first seizure. Brain imaging studies revealed on the left an extra-axial thickening of the dura mater with enhancement and perilesional oedema, infiltrating the sphenoorbital fissure and an isointense mass with enhancement in the orbital region with dislocation of the optic nerve. Pathological and immunohistochemistry examination of the bioptical specimen was consistent with a diagnosis of RDD. Treatment with levetiracetam and steroids was started obtaining only remission of seizures. Because of the patient refusal of the surgical debulking, therapy with mercaptopurine was started, stopping disease progression. Conclusion. So far, very few cases of extranodal RDD with multiple CNS lesions involving the orbital region have been described. Our case is significant because it is the first case in which the efficacy of mercaptopurine treatment has been documented in an adult patient with isolated ocular and intracranial RDD.

Corticobasal syndrome-like variant of Creutzfeldt–Jakob disease: clinical description of two cases

‘‘It Seemed to have a life of its own’’. This is how the first patient with Creutzfeldt–Jakob disease (CJD) described his alien limb [1]. CJD is clinically heterogeneous because several rare phenotypes have been associated with the wide spectrum of sCJD [2]. Corticobasal syndrome (CBS) can occur in neurodegenerative disease (Alzheimer’s disease and parkinsonism) including CJD (sCJD-CBS). Although, no specific clinical features that reliably predict underlying pathology in CBS have been described, common clinical observations of sCJDCBS include limb apraxia, dysphasia, sensory loss, neglect syndrome, myoclonus, dystonia, rigidity, bradykinesia, ataxia of gait, pyramidal symptoms and cognitive impairment [3, 4]. Alien limb phenomena might represent an early clinical manifestation of the sCJD-CBS clinical subtype. Here, we describe two cases of sCJD-CBS presenting dominant posterior-variant alien hand syndrome and aphasia. Case one A 55-year-old, right-handed male was referred to our hospital after a 2-month history of aphasia nominum associated with rapidly progressive cognitive impairment. He was found to have an alien limb syndrome of the right arm. A first brain MRI resulted normal. Over the next two weeks, there was a worsening in aphasia, progressively involving both speech and comprehension. The patient went on to develop agraphia, acalculia, urinary incontinence, behavioural disorders and loss of balance. Two weeks later, a spontaneous myoclonus in his right arm appeared. EEG showed diffuse theta–delta slowing but no periodical sharp waves. A second brain MRI revealed an extensive and diffuse DWI hyperintense signal in the caudate and lenticular nuclei, the posterior temporal, occipital, posterior parasagittal parietal and cingulate gyrus cortices on the left hemisphere. These same areas were hypointense on the apparent diffusion coefficient (ADC) map. 14-3-3 protein was detected in cerebrospinal fluid (CSF). Prion protein (PrP) gene analysis revealed only a Met/Met genotype at codon 129. Four months after disease presentation, the patient died. Case two A 65-year-old, right-handed, female with history of hypertension, complained of an inability to use her right hand and gait instability over the course of the last two months. On admission, she was found to have language impairment with aphasia nominum, dystonia, ideomotor apraxia and mild rigidity affecting her right arm. Over the next days, loss of balance, myoclonus began to occur. An MRI showed DWI hyperintensities involving the left caudate nucleus and putamen and bilateral (but predominantly on the left) parietal, insular, frontal parasagittal, occipital cortices; all which appeared hypointense in ADC map. EEG showed diffuse slowing with periodic lateralized V. Arnao M. Gangitano F. Giacalone M. Riolo G. Savettieri P. Aridon (&) Dipartimento di BioMedicina Sperimentale e Neuroscienze Cliniche, Università degli Studi di Palermo, Via Gaetano La Loggia n.1, 90144 Palermo, Italy e-mail: paolo.aridon@unipa.it

A case of recurrent stroke due to late onset antiphospholipid syndrome

Dear Editor, Worldwide stroke is a leading cause of mortality and disability both in old and young people. In the elderly, cerebrovascular events are more frequent in patients with underlying vascular risk factors, such as hypertension, diabetes, cervical vessels atherosclerosis, and atrial fibrillation. Nevertheless, a likely cause cannot be detected for a consistent percentage of stroke and, therefore, they are considered cryptogenic ones; a relevant proportion of so-called cryptogenic strokes may be due to undetected paroxysmal atrial fibrillation. The high frequency of stroke risk factors in the elderly makes more extensive search not mandatory in this population, whereas stroke in younger patients leads to thorough investigation including thrombophilia and autoimmunity tests as well as the evaluation of intracranial vessels. We report a case of a recurrent stroke due to a typically juvenile cause in a 78-year-old Caucasian man. The patient had a history of hypertension, diabetesmellitus, hypercholesterolemia, and mild renal insufficiency. In March 2016, he had an ischaemic stroke in the right temporo-insular and posterior frontal region, with partial recovery (he was able to walk with a stick due to reduced strength in his left leg). After diagnostic studies (including blood tests, echocardiography, Holter-ECG, cervical arteries, and transcranial ultrasound), no underlying reason of the event was found and the patient was discharged home with antiplatelet treatment (acetylsalicylic acid 100 mg/die). Two months later, he had another cerebrovascular event characterized by left central facial palsy and paresis in left limbs got worse. At the emergency department, a brain CT scan was performed, showing only the presence of the previous ischaemic lesion. The neurological examination revealed left inferior quadrantanopia, dysarthria, and left hemiparesis. At admission, his NIHSS was eight. However, after a few days, his strength deficit worsened and he gradually developed left hemiplegia. A control CT after 2 days showed an extension of the previous ischaemic lesion to the posterior frontal lobe (F1) and right central part of corpus callosum. Cervical vessels Doppler showed a non-significant stenosis in bilateral carotid bifurcation. The study of intracranial vessels with transcranial color Doppler (TCCD) was normal. ECG showed a sinusal rhythm and Holter-ECG registered the same. A transesophageal echocardiography was performed in order to rule out anatomical alterations suggestive for paroxysmal atrial fibrillation or cardiac structure abnormalities, as a cause of the recurrent stroke, but it was negative. A complete blood analysis was normal except for the presence of anticoagulans (LAC), ANA 1:160, dsDNA autoantibody (20 IU/ml), IgG antibody against cardiolipin (aCL) (225 IU/ml) and antibeta2-glycoprotein (anti-β2GPI) IgG (89 IU/ml). Therefore, with a strong suspicion of a diagnosis of antiphospholipid syndrome, treatment with warfarin (INR target 2.0–3.0) was started. This idea was supported by the fact that elevated levels of LC and aCL could not be secondary to infection or malignancy, because these conditions had been excluded with clinical examination, imaging, and laboratory tests. However, after 2 months in a rehabilitation structure with little clinical improvement, the patient died 3 weeks after * Andrea Salmaggi a.salmaggi@asst-lecco.it

New frontiers in anticoagulation: non vitamin-K oral anticoagulants in stroke prevention

ABSTRACT Introduction: Non vitamin-K oral anticoagulants (NOACs) are direct and specific inhibitors of the coagulation factors IIa (dabigatran) and Xa (apixaban, rivaroxaban, edoxaban) which share many pharmacokinetic properties. However, indications are lacking regarding the use of NOACs during thrombolysis, surgery and bleeding events. Areas covered: In this paper, the authors retrospectively analyzed the relevant literature on the NOACs using the PubMed and Google Scholar databases. Expert commentary: Although warfarin is effective in cardioembolic stroke prevention, easier handling and more favorable risk-benefit profile often render NOACs a more preferable therapy choice for neurologists. New evidences have suggested their use in treatment of elderly people, in patients with renal insufficiency or with antiphospholipid antibody syndrome. In addition, the use of antidotes, which rapidly reverse the anticoagulant effect of the NOACs, could be useful in bleeding, during emergency procedures, or in case of overdose.

Seizure following the Use of the COX-2 Inhibitor Etoricoxib

We describe a case of epileptic seizures occurring after the use of a COX-2 inhibitor. A 61-year-old man was admitted to our department because of a generalized tonic-clonic seizure. EEG showed generalized slowdown of the activity. Neuroimaging and blood samples studies did not evidence alterations, but a careful pharmacological history revealed that the patient had taken the COX-2 inhibitor etoricoxib to treat lumbago few days before the onset of clinical symptoms. No seizures were reported after etoricoxib discontinuation and an EEG resulted to be normal two months after this. Conclusion. Knowing the pharmacological history of a patient is important for understanding the clinical presentation and selecting appropriate treatment. This is, to the best of our knowledge, the first reported case of generalized seizures associated with the use of COX-2 inhibitors.

A case of unusually long survival after leptomeningeal carcinomatosis diagnosis

Relating to the letter “Leptomeningeal carcinomatosis 9 years after nodule resection for pulmonary carcinoma in situ: MRS and pathological studies” reported in your September 2017, Vol 34, Issue 2, we agree that leptomeningeal metastases (LM) are difficult to diagnose, and, when this occurs, patient’s prognosis is poor with a median overall survival of 3,3 months from the time of the diagnosis [1, 2]. Nevertheless, some reports describe a sporadic long survival. Here, we chronicle a case of LM with a long survival despite the poor-risk profile according to present treatment guidelines. On September 2017 a 74-year-old woman came to our department because she had an episode of loss of consciousness while she was lying in bed, associated with clonic limb jerks, lasting few minutes and followed by post-ictal confusional state. The patient had a history of breast cancer (diagnosed in 1985, at age 43), for which a left mastectomy was performed, with a scar relapse 3 years later, treated with radio and chemotherapy (RT and CT). After that, she was well and led a normal life, even if in 2001 she noticed the occurence of a hypotrophy in her left arm, which, however, was not related to a motor dysfunction. In 2011 she was hospitalized due to an episode of hypertension and, during her stay, she complained about left leg weakness and walking difficulties, for which she needed bilateral support. For this reason a brain and spine gadolinium-enhanced MRI was performed, revealing the presence of diffuse leptomeningeal contrast along optic chiasm, V, VII, VIII cranial nerves, conus and cauda, with an initial increase in lateral ventricular size, indicating possible leptomeningeal metastasis. CSF analysis showed high protein concentration (355 mg/dl) and lymphocytic pleocytosis (43/mm3), but cytology was not positive for the presence of malignant cells. Because thoracic and abdomen CT scan were negative for metastatic disease, a total body PET was performed and it revealed the presence of bone metastasis at the fifth thoracic vertebral level (T5). A biopsy was performed and it revealed the presence of epithelial cells attributable to breast cancer with expression of both estrogen (80–90%) and progesterone (80–85%) receptors; consequently, she underwent to focal RT at T5 level (20 Gy given in five times). Hormonal therapy with letrozole was started. A repeated CSF analysis still showed a lymphocytic pleocytosis with the presence of bigger cells with hyperbasophilic cytoplasm and irregular boundaries positive for cytokeratin; intrathecal CEA synthesis was detected (Fig. 1a). Evaluation of HSV, VZV, EBV, CMV, toxoplasma PCR, serology for HIV 1–2, and CSF cultural samples were negative. A diagnosis of LM was confirmed and—despite low KPS (50)—in view of good cognitive status and fairly controlled extracranial disease— she was treated with intrathecal chemotherapy with lyposomal cytarabine for five cycles (50 mg each time). After this well-tolerated therapy the patient was clinically stable for 6 years, except for rachialgia, due to which she overtook non-steroidal-anti-inflammatory drugs. During the last hospitalization, she still needed a walker and she developed urinary retention, requiring urethral catheterization. Brain and spine MRI (Fig. 2) showed an increase in ventricular size, while the known leptomeningeal nodules were unchanged; CSF analysis showed the presence of tumoral cells (Fig. 1b). She was dismissed home and her performance status was 40. In this case, the diagnosis of LMC was supported by clinical, radiological and laboratoristic criteria. In particular, the detection of intrathecal CEA synthesis is highly sensitive * Andrea Salmaggi a.salmaggi@asst-lecco.it

Frontal dementia related to thalamic stroke: a case report.

The behavioral variant of frontotemporal dementia (bvFTD) is characterized by modifications of personality, social behavior and cognition and relies on a neurodegenerative process [1]. However, vascular lesions affecting subcortical structures, mainly the caudate nucleus and thalamus, may result in a clinical syndrome resembling bvFTD [2, 3]. We report a case of paramedian thalamic stroke mimicking frontotemporal dementia. A 58-year-old righthanded man was referred to our hospital because of behavioral and cognitive changes formerly diagnosed as bvFTD. His medical history was negative for previous illness and the patient neither smoked nor drank alcohol. In July 2010, the patient suddenly presented with loss of consciousness and was admitted to a nearby hospital. After a few days the decreased level of consciousness resolved and he developed amnesia and personality changes such as disinhibition, apathy and loss of selfactivation. Toxicological exams, routine CSF analysis including total proteins, count cell, glucose and CSF culture were normal at admission. CT scan performed within twelve hours the onset of disturbances was also normal. The patient was diagnosed as affected by a conversion disorder. Because of the disturbances, the patient left his job and moved to live with his sister since he was not able to care for himself. After 6 months, the patient was submitted to a neuropsychological screening, showing an impairment of executive functions and amnesia. A diagnosis of frontotemporal dementia was supposed. The patient was referred to our Center in January 2011. The neurological examination was normal. Neuropsychological tests confirmed an alteration of executive functions as well as verbal and visual memory deficits. This was coupled with behavioral disturbances of apathy and depression. Brain MRI showed a mild frontotemporal atrophy with ventricular dilatation but also a left thalamic infarct in the paramedian territory (Fig. 1). The patient started therapy with paroxetine (20 mg/day) and memantine (10 mg/day). At 6-month and 1-year, follow-up neuropsychological test showed a further recovery of cognitive functions and behavioral disturbances (Table 1). The caregivers also reported a gradual improvement of disturbances since the onset. Brain CT confirmed thalamic infarction. We made a diagnosis of a thalamic stroke as the cause of dementia, because of the sudden onset and the gradual improvement of the clinical syndrome and the correspondent finding of an ischemic lesion. Routine blood tests, hemocoagulative screening and autoantibody pattern were normal. Electrocardiogram and carotid ultrasonography did not show any alterations. The transthoracic echocardiogram, the transcranial Doppler sonography and the transoesophageal echocardiography detected the patent foramen ovale (PFO) and the patient was started anticoagulant therapy. After 2 years, the S. Realmuto (&) V. Arnao A. Cinturino M. A. Mazzola S. Talamanca M. Riolo I. Cusmano C. Cupidi T. Piccoli Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche (BioNeC), Università degli Studi di Palermo, Via Gaetano La Loggia no 1, Palermo, Italy e-mail: sabrinarealmuto@gmail.com