Frequency and Characterization of Movement Disorders in Anti-IgLON5 Disease.

OBJECTIVE: Anti-IgLON5 disease is a recently described neurological disease that shares features of autoimmunity and neurodegeneration. Abnormal movements appear to be frequent and important but have not been characterized and are under-reported. Here we describe the frequency and types of movement disorders in a series of consecutive patients with this disease. METHODS: In this retrospective, observational study, the presence and phenomenology of movement disorders were assessed with a standardized clinical questionnaire. Available videos were centrally reviewed by three experts in movement disorders. RESULTS: Seventy two patients were included. In 41 (57%) the main reason for initial consultation was difficulty walking along with one or several concurrent movement disorders. At the time of anti-IgLON5 diagnosis, 63 (87%) patients had at least one movement disorder with a median of three per patient. The most frequent abnormal movements were gait and balance disturbances (52 patients, 72%), chorea (24, 33%), bradykinesia (20, 28%), dystonia (19, 26%), abnormal body postures or rigidity (18, 25%), and tremor (15, 21%). Other hyperkinetic movements (myoclonus, akathisia, myorhythmia, myokymia, or abdominal dyskinesias) occurred in 26 (36%) patients. The craniofacial region was one of the most frequently affected by multiple concurrent movement disorders (23 patients, 32%) including dystonia (13), myorhythmia (6), chorea (4) or myokymia (4). Considering any body region, the most frequent combination of multiple movement disorders consisted of gait instability or ataxia associated with craniofacial dyskinesias or generalized chorea observed in 31(43%) of patients. In addition to abnormal movements, 87% of patients had sleep alterations, 74% bulbar dysfunction, and 53% cognitive impairment. Fifty-five (76%) patients were treated with immunotherapy, resulting in important and sustained improvement of the movement disorders in only seven (13%) cases. CONCLUSIONS: Movement disorders are a frequent and leading cause of initial neurological consultation in patients with anti-IgLON5 disease. Although multiple types of abnormal movements can occur, the most prevalent are disorders of gait, generalized chorea, and dystonia and other dyskinesias that frequently affect craniofacial muscles. Overall, anti-IgLON5 disease should be considered in patients with multiple movement disorders, particularly if they occur in association with sleep alterations, bulbar dysfunction, or cognitive impairment.

Clinical manifestations of the anti-IgLON5 disease.

OBJECTIVE: To report the presentation, main syndromes, human leukocyte antigen (HLA) association, and immunoglobulin G (IgG) subclass in the anti-IgLON5 disease: a disorder with parasomnias, sleep apnea, and IgLON5 antibodies. METHODS: This was a retrospective clinical analysis of 22 patients. The IgG subclass was determined using reported techniques. RESULTS: Patients' median age was 64 years (range 46-83). Symptoms that led to initial consultation included sleep problems (8 patients; 36%), gait abnormalities (8; 36%), bulbar dysfunction (3; 14%), chorea (2; 9%), and cognitive decline (1; 5%). By the time of diagnosis of the disorder, 4 syndromes were identified: (1) a sleep disorder with parasomnia and sleep breathing difficulty in 8 (36%) patients; (2) a bulbar syndrome including dysphagia, sialorrhea, stridor, or acute respiratory insufficiency in 6 (27%); (3) a syndrome resembling progressive supranuclear palsy (PSP-like) in 5 (23%); and (4) cognitive decline with or without chorea in 3 (14%). All patients eventually developed parasomnia, sleep apnea, insomnia, or excessive daytime sleepiness. HLA-DRB1*10:01 and HLA-DQB1*05:01 were positive in 13/15 (87%) patients; the DRB1*10:01 allele was 36 times more prevalent than in the general population. Among 16 patients with paired serum and CSF samples, 14 had IgLON5 antibodies in both, and 2 only in serum (both had a PSP-like syndrome). Twenty of 21 patients had IgG1 and IgG4 antibodies; the latter predominated in 16. CONCLUSIONS: Patients with IgLON5 antibodies develop a characteristic sleep disorder preceded or accompanied by bulbar symptoms, gait abnormalities, oculomotor problems, and, less frequently, cognitive decline. IgG4 subclass antibodies predominate over IgG1; we confirm a strong association with the HLA-DRB1*10:01 allele.

Idiopathic Ophthalmodynia and Idiopathic Rhinalgia: A Prospective Series of 16 New Cases.

BACKGROUND: Idiopathic ophthalmodynia and idiopathic rhinalgia were described a few years ago. These conditions seem specific pain syndromes with a distinctive location in the eye or in the nose. We aimed to present a new prospective series in order to verify the consistency of these syndromes. METHODS: We performed a descriptive study of all patients referred to our regional neurologic clinics from 2010 to 2014 because of facial pain exclusively felt in the eye or in the nose fulfilling the proposed diagnostic criteria for idiopathic ophthalmodynia and idiopathic rhinalgia. RESULTS: There were 9 patients with idiopathic ophthalmodynia and 7 patients with idiopathic rhinalgia, with a clear female preponderance, and a mean age at onset in the fifth decade. The pain was usually moderate and the temporal pattern was generally chronic. Only one patient reported accompaniments (hypersensitivity to the light and to the flow of air in the symptomatic eye). Preventive treatment with amitriptyline, pregabalin, or gabapentin was partially or totally effective. CONCLUSIONS: The clinical features of this new series parallels those of the original description, thus indicating that both idiopathic ophthalmodynia and idiopathic rhinalgia have clear-cut clinical pictures with excellent consistency both inter- and intra-individually.

Unilateral nasal pain with migraine features.

BACKGROUND: Migraine attacks exclusively felt in the face are very rare, the pain involving the territories supplied by the second and third branches of the trigeminal nerve. CASES: Two patients suffering from heminasal pain attacks accompanied with typical migrainous features and responsive to oral or intranasal triptans - but not to intranasal lidocaine or oxymetazoline. In one patient, the attacks could be precipitated upon slight touching on the tip of the nose, in the other attacks were preceded by the nasal sensation typically heralding sneezing. DISCUSSION: Migraine pain mostly develops within the innervation territory of the first branch of the trigeminal nerve, which includes the nose. Therefore, episodes of unilateral nasal pain with migrainous features could be considered a migraine with unusual topography (nasal migraine). Painful nasal attacks occasionally preceded by stimulation of trigeminal afferents in the nose, could be conceived of as migraine-tic syndrome.

SUNCT and SUNA: Recognition and Treatment.

OPINION STATEMENT: The problem of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) management remains unsolved. Despite a myriad of therapeutic trials, no convincingly effective remedy for SUNCT and SUNA is available at present. Based on open-label communications, some patients seemed to benefit from some pharmacologic, interventional, or invasive procedures. Possible effective preventive drugs are carbamazepine, lamotrigine, gabapentin, and topiramate. At present, the drug of choice for SUNCT seems to be lamotrigine whereas SUNA may better respond to gabapentin. There is no available abortive treatment for the individual attacks. During the worst periods, intravenous lidocaine may decrease the flow of SUNCT/SUNA attacks. In SUNCT, bilateral blockade of the greater occipital nerve, and superior cervical ganglion opioid blockade have been reported as temporary/partially effective in one patient each. Botulinum toxin injected around the symptomatic orbit provided sustained relief to one patient. Owing to the scarcity of reports the results of these interventions should be taken as preliminary. Invasive therapy with interventions directed to the first division of the trigeminal nerve or Gasserian ganglion, with local anesthetics or alcohol, radiofrequency thermocoagulation, microvascular decompression, and gamma-knife neurosurgery, have been tried in the treatment of refractory SUNCT. Some patients seemed to benefit from such interventions, but one should still have a critical attitude to these claims since no convincing results have been obtained as yet. The few SUNCT patients who underwent deep brain hypothalamic stimulation obtained a substantial and persistent relief.

Primary continuous unilateral headaches: a nosologic model for hemicrania continua.

BACKGROUND: Hemicrania continua was originally described as a strictly unilateral, continuous headache with an absolute response to indomethacin. Recognition of an increasing number of patients with the same clinical features except for a lack of response to indomethacin has generated controversy about whether the responsive/non-responsive phenotypes belong to the same disorder. DISCUSSION: We suggest that the non-responsive phenotype should be differentiated from the original concept of hemicrania continua, because it probably indicates a separate type of headache of undetermined nature, i.e. hemicrania incerta. However, differentiating hemicrania incerta from hemicrania continua does not imply that the two headaches are unrelated. Both hemicranias may outline a continuum, giving rise to a broader diagnostic field. CONCLUSION: There seems to be a syndrome of 'primary continuous unilateral headache' with at least two distinctive categories: hemicrania continua and hemicrania incerta, which are differentiated by their respective response to indomethacin. This division means plurality but adds precision, and allows a clear-cut diagnosis of some controversial cases.

Nummular headache update.

Nummular headache is characterized by head pain exclusively felt in a rounded or elliptical area, typically 1 to 6 cm in diameter. The pain remains confined to the same symptomatic area, which does not change in shape or size with time. The symptomatic area may be localized in any part of the head but mostly in the parietal region. Rarely, the disorder may be multifocal, each symptomatic area keeping all the characteristics of nummular headache. The pain is generally mild or moderate, commonly described as oppressive or stabbing, and lasting minutes, hours, or days, with a remitting or unremitting pattern. Superimposed on the baseline pain, there may be spontaneous or triggered exacerbations. During and between symptomatic periods, the affected area may show variable combinations of hypoesthesia, dysesthesia, paresthesia, tenderness, and trophic changes. Nummular headache emerges as a primary disorder with a clear-cut clinical picture developed in a unique topography.