Pachymeningeal involvement in POEMS syndrome: MRI and histopathological study.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome is a rare plasma cell disease. Vascular endothelial growth factor (VEGF) seems to play a pathogenic role. Peripheral neuropathy is the main neurological feature. Cranial pachymeningitis has occasionally been reported, but no histopathological studies have been performed. The authors extensively evaluated the central nervous system MRI in 11 patients (seven men, four women; mean age at diagnosis 54.45 years) with POEMS syndrome. In two patients, meningeal histopathology with staining for VEGF and VEGF receptor was performed, and pachymeningeal involvement characterised at histopathological, immunohistochemical and confocal microscopy levels. Nine patients presented with cranial pachymeningitis. One patient suffered from migraine, and none complained of cranial nerve palsies or visual loss. None showed any MRI signs of spinal pachymeningitis. No correlation was found with disease duration and VEGF serum level. Histopathology showed hyperplasia of meningothelial cells, neovascularisation and obstructive vessel remodelling, without inflammation. VEGF and VEGF receptor were strongly coexpressed on endothelium, smooth-muscle cells of arterioles and meningothelial cells. In conclusion, POEMS patients present a high prevalence of meningeal involvement. The histological changes, different from those present in chronic pachymeningitis of other aetiology, suggest a possible VEGF role in the pathogenesis of the meningeal remodelling.

A critical reflection on our first patient presenting with Anti-Nmethyl- D-aspartate receptor encephalitis.

One of the best characterized autoimmune encephalitis is the Anti-Nmethyl- D-aspartate receptor (NMDAR) encephalitis, which may occur in the presence of cancer. First- and second-line immunotherapy and oncological investigations are suggested. We present here a case of an 18-year-old female who was our first patient suffering from Anti- NMDAR encephalitis more than 9 years ago. She was satisfactorily treated with intravenous immunoglobulins and high dose steroid therapy. After more than one year the patient had a relapse. First-line immunotherapy was repeated; however, a complete recovery was achieved only after plasmapheresis. Afterwards, she continued maintenance immunotherapy with steroids for two years and with Azathioprine for about five years associated to regular oncological assessment. In the last years our therapeutical approach of Anti-NMDARencephalitis has significantly changed. Nevertheless, established treatment guidelines are still missing and the role of long-term maintenance immunotherapy is largely unexplored. In addition, oncological revaluation might be indicated in selected patients.

Stiff Person Syndrome: A Rare Neurological Disorder, Heterogeneous in Clinical Presentation and Not Easy to Treat.

Background. Stiff person syndrome (SPS) is a rare neurological disorder characterized by progressive rigidity of axial and limb muscles associated with painful spasms. SPS can be classified into classic SPS, paraneoplastic SPS, and SPS variants. Its underlying pathogenesis is probably autoimmune, as in most cases antibodies against glutamic acid decarboxylase (GAD) are observed. Similarly, paraneoplastic SPS is usually linked to anti-amphiphysin antibodies. Treatment is based on drugs enhancing gamma-aminobutyric acid (GABA) transmission and immunomodulatory agents. Case Series. Patient 1 is a 45-year-old male affected by the classic SPS, Patient 2 is a 73-year-old male affected by paraneoplastic SPS, and Patient 3 is a 68-year-old male affected by the stiff limb syndrome, a SPS variant where symptoms are confined to the limbs. Symptoms, diagnostic findings, and clinical course were extremely variable in the three patients, and treatment was often unsatisfactory and not well tolerated, thus reducing patient compliance. Clinical manifestations also included some unusual features such as recurrent vomiting and progressive dysarthria. Conclusions. SPS is a rare disorder that causes significant disability. Because of its extensive clinical variability, a multitask and personalized treatment is indicated. A clearer understanding of uncommon clinical features and better-tolerated therapeutic strategies are still needed.

Trigemino-cervical reflex abnormalities in patients with migraine and cluster headache.

BACKGROUND: Head pain arises within the trigeminal nociceptive system. Current theories propose that the trigeminal system is intimately involved in the pathogenesis of migraine. Short-latency responses can be recorded in sternocleidomastoid muscles after stimulation of the trigeminal nerve (trigemino-cervical reflex). This brainstem reflex could be a suitable method to evaluate the trigeminal system in migraine and CH. OBJECTIVE: The aim of the present study was to further elucidate the pathophysiology of migraine and cluster headache (CH) with special reference to the involvement of the central trigeminal system in the different forms of primary headache. METHODS: The trigemino-cervical reflex was investigated in 15 healthy subjects, in 15 patients having migraine with aura, in 15 patients with migraine without aura, and in 10 patients with CH. RESULTS: Significant abnormalities were observed in a great number of patients with both types of migraine and CH during the headache attacks, but only in migraine patients during the interictal period. The alterations are bilateral in migraine, unilateral in CH. CONCLUSIONS: Our results further support the relevance of brainstem mechanisms in the pathogenesis of migraine rather than of CH. These data, taken together with that from experimental head pain and functional imaging studies, demonstrate that primary headache syndromes may be distinguished on a functional basis by areas of activation specific to the clinical syndrome.

Cholinergic cortical circuits in Parkinson's disease and in progressive supranuclear palsy: a transcranial magnetic stimulation study.

To investigate the involvement of the cortical cholinergic system in patients with Parkinson's disease (PD) and with progressive supranuclear palsy (PSP), we performed a comparative study of the short latency afferent inhibition (SAI) in ten patients with PD, in eight patients with PSP and in 15 healthy subjects. Six of the PD patients and four of the PSP patients had dementia. SAI was significantly increased in the PD patients, whereas it was not significantly different between PSP patients and the normal controls. Our findings demonstrate that the excitability of the motor cortex is differentially modulated by sensory afferents in PD and PSP and may indicate that the mechanisms of cholinergic dysfunction are different between the two diseases.