Mohammad Hassan A. Noureldine

Hughes syndrome and Multiple sclerosis

Multiple sclerosis (MS) and antiphospholipid syndrome (APS) share common clinical, laboratory and radiological features. We reviewed all the English papers on MS and APS published in the literature from 1965 to 2014 using PubMed and Google Scholar. We found that APS can mimic antiphospholipid antibodies (aPL)-positive MS in many ways in its clinical presentation. Nevertheless, APS diagnosis, clinical manifestations and management differ from those of MS. aPL were found in MS patients with titers ranging from 2% to 88%. The distribution and volume of lesions on magnetic resonance imaging (MRI) may help to differentiate MS from primary APS. In addition, atypical MS presentation can guide physicians toward an alternative diagnosis, especially when features of thrombosis and/or history of connective tissue disease are present. In that case, an anticoagulation trial could be worthwhile.

Antiphospholipid syndrome (APS) revisited: Would migraine headaches be included in future classification criteria?

Abstract Headaches have been extensively reported in Antiphospholipid syndrome (APS)/Antiphospholipid antibodies (aPL)-positive patients. The aim of this study was to highlight the prevalence of headaches among APS/aPL-positive patients and discuss its association with laboratory, clinical and imaging findings. We searched the literature through Google Scholar and PubMed for publications on the epidemiology, pathogenesis, laboratory, imaging and clinical findings, and management of headaches in APS/aPL-positive patients. The following keywords were used: Antiphospholipid, Hughes syndrome, anticardiolipin, lupus anticoagulant, anti-β2 glycoprotein I, headache, migraine, tension, and cluster. All reports published between 1969 and 2015 were included. Migraine is the most commonly reported type of headache in APS/aPL-positive patients. Thrombotic and platelet dysfunction hypotheses have been studied to uncover the pathogenic role of aPL in the development of headaches. Several studies are reporting higher levels of aPL in primary and secondary APS migraineurs, but only few reached statistical significance. Migraine patients without clinical signs/symptoms of cerebral infarction rarely show positive imaging findings. Digital subtraction angiography shows promise in demonstrating small vascular lesions otherwise not detected on computed tomography, magnetic resonance imaging, or cerebral angiograms. Although it may be solitary and harmless in many cases, the deleterious effect of migraine on the quality of life of APS patients prompts rapid diagnosis and proper management. An anticoagulation trial is advisable in APS patients with migraine as many cases of severe, refractory migraine resolved with anticoagulation therapy. The profile of migraine headaches discussed in this study permits its candidacy for inclusion in future APS classification criteria.

Hughes syndrome and epilepsy: when to test for antiphospholipid antibodies?

Epilepsy and seizures are reported among the neurological manifestations of antiphospholipid syndrome (APS) at a prevalence rate of approximately 8%, which is nearly 10 times the prevalence of epilepsy in the general population. The association of seizures with antiphospholipid antibodies (aPL) is even more significant in the presence of systemic lupus erythematosus (SLE). In this review, we discuss the epidemiological, pathophysiological, laboratory, clinical, and radiological aspects of this association, and derive suggestions on when to consider testing for aPL in epileptic patients and how to manage seizures secondary to APS based on literature data. Epilepsy due to APS should be considered in young patients presenting with seizures of unknown origin. Temporal lobe epilepsy seems to be particularly prevalent in APS patients. The pathogenesis is complex and may not only involve micro-thrombosis, but also a possible immune-mediated neuronal damage. Patients with seizures and positive aPL tend to develop thrombocytopenia and livedo racemosa more frequently compared with those without aPL. Magnetic resonance imaging (MRI) remains the imaging modality of choice in these patients. The presence of SLE and the presence of neurological symptoms significantly correlate with the presence of white matter changes on MRI. In contrast, the correlation between aPL positivity and the presence of white matter changes is very weak. Furthermore, MRI can be normal in more than 30–40% of neuropsychiatric lupus patients with or without aPL. aPL testing is recommended in young patients presenting with atypical seizures and multiple hyper-intensity lesions on brain MRI in the absence of other possible conditions. New MRI techniques can better understand the pathology of brain damage in neuro-APS. The therapeutic management of epileptic APS patients relies on anti-epileptic treatment and anticoagulant agents when there is evidence of a thrombotic event. In the absence of consensual recommendations, the decision of lifelong anticoagulation is discussed on a case-by-case basis. The anti-thrombotic benefit of hydroxychloroquine and statins is supported by several studies.

Arterial stenosis in antiphospholipid syndrome: Update on the unrevealed mechanisms of an endothelial disease

First described in 1983, antiphospholipid syndrome (APS) is an autoimmune condition characterized by the occurrence of recurrent arterial and/or venous thrombosis, and/or pregnancy morbidity, in the setting of persistent presence of antiphospholipid antibodies (aPL). While thrombosis is the most well-known pathogenic mechanism in this disorder, the relevance of some other mechanisms such as arterial stenosis is being increasingly recognized. Arterial stenosis has been first described in the renal arteries in patients with APS, however intracranial and coeliac arteries can also be involved with various and treatable clinical manifestations. The underlying pathophysiology of this stenotic arterial vasculopathy is not fully understood but some recent studies revealed new insights into the molecular mechanism behind this endothelial cell activation in APS. In this review, we discuss these newly discovered mechanisms and highlight the diagnostic and therapeutic modalities of the APS related arterial stenosis.

Musculoskeletal manifestations of the antiphospholipid syndrome.

The scope of clinical and laboratory manifestations of the antiphospholipid syndrome (APS) has increased dramatically since its discovery in 1983, where any organ system can be involved. Musculoskeletal complications are consistently reported in APS patients, not only causing morbidity and mortality, but also affecting their quality of life. We reviewed all English papers on APS involvement in the musculoskeletal system using Google Scholar and Pubmed; all reports are summarized in a table in this review. The spectrum of manifestations includes arthralgia/arthritis, avascular necrosis of bone, bone marrow necrosis, complex regional pain syndrome type-1, muscle infarction, non-traumatic fractures, and osteoporosis. Some of these manifestations were reported in good quality studies, some of which showed an association between aPL-positivity and the occurrence of these manifestations, while others were merely described in case reports.

Nonclassification Criteria Manifestations of the Antiphospholipid Syndrome

Abstract The volume and quality of knowledge about Hughes or the antiphospholipid syndrome (APS) has significantly improved since its first appearance in the 1980s. The first APS classification criteria was established in Sapporo, Japan, and was amended in Sydney, Australia, 7 years later. In addition to the classification criteria, the congress members in both meetings generally agreed that a set of APS features – now termed nonclassification criteria – are frequently reported, but their association with the disease was not significant enough to permit inclusion in the classification criteria. These features vary from noncriteria obstetrical (clinical and laboratory), haematologic (thrombocytopenia, superficial vein thrombosis), dermatologic (livedo reticularis/racemosa), cardiac (valve disease), renal (thrombotic disease), and neurologic (migraine, seizures, cognitive dysfunction, chorea, transverse myelitis) manifestations. The goal of this chapter is to highlight the significance of nonclassification criteria manifestations of APS based on clinical, observational, and experimental studies performed after the Sydney International workshop, in addition to recommendations issued by the International Congresses on antiphospholipid syndrome.

Ankylosing Spondylitis among Familial Mediterranean Fever Patients

BACKGROUND Familial Mediterranean Fever (FMF) is one of the most common hereditary auto-inflammatory diseases especially among Arabs, Armenians, Jews, and Turks characterized by recurrent attacks of fever, abdominal pain and arthritis.Whether the prevalence of ankylosing spondylitis (AS) is increased in FMF patients is a matter of debate. This review will summarize all the literature data relevant to this topic. METHODS We searched all the articles through PubMed and Embase databases from 1963 until 2017 addressing the relationship between AS and FMF patients. RESULTS The prevalence of AS among FMF patients is highly variable. However, a significant relationship was found to exist between MEFV gene mutations and AS. Most patients with coexistent MEFV gene mutations and AS were human leucocyte antigen B27 (HLA-B27) negative. The effect of these mutations on AS severity and prognosis was not significant. CONCLUSION Large based population studies are needed to further assess the existence of MEFV gene mutations among AS patients and their effect on the clinical course of the disease in addition to assessment of AS prevalence in patients with FMF.

The ulnar ratio as a sensitive and specific marker of acute inflammatory demyelinating polyneuropathy

OBJECTIVES To explore the value of a novel sensory criterion, the ulnar ratio - defined as the SNAP amplitude of the palmar cutaneous (pUN) over that of the dorsal branch (dUN) of the ulnar nerve - as a predictor of Acute Inflammatory Demyelinating Polyneuropathy (AIDP). METHODS We prospectively included 22 patients with AIDP, 20 patients with diabetic peripheral neuropathy (DPN), and 18 controls. Eligible subjects underwent nerve conduction studies including, among others, the dUN, pUN, and sural nerve. RESULTS A sural sparing pattern was found in 72% of AIDP cases. The ulnar ratio was significantly lower in patients with AIDP compared to those with DPN or controls. The ROC curve area to discriminate AIDP (versus controls and diabetics together) was higher with the ulnar ratio and pUN compared to dUN. An ulnar ratio ≥ 0.78 seems to be the best threshold to rule out the diagnosis of AIDP, with a specificity of 100% and a sensitivity of 87%. The ulnar ratio was equally reliable in the subgroup of patients presenting within a week of symptoms onset. CONCLUSION The ulnar ratio is a highly sensitive and specific marker of AIDP and can help confirm the diagnosis when direct signs of demyelination are lacking. SIGNIFICANCE Incorporating specific sensory abnormalities, such as the ulnar ratio, in the electrodiagnostic criteria of AIDP could enhance their reliability.

Hyperacoustic hypoacusis: A new pontine syndrome—Case report

ABSTRACT We herein report a unique case of a lateral pontine demyelinating lesion presenting with unilateral sensorineural hearing loss and paradoxical ipsilateral hyperacusis. The association of unilateral hearing loss and ipsilateral hyperacusis is a rare manifestation of a central nervous system lesion. The paradoxical combination of these symptoms strongly suggests pontine dysfunction and prompts urgent neurological evaluation.

Miller Fisher syndrome presenting as palate paralysis

We report a 63-year old patient who presented to our care initially with a hypernasal voice followed by ataxia, ptosis, dysphonia, and paresthesias. The patients history, physical examination, and additional tests led to a Miller Fisher syndrome (MFS) diagnosis. Palatal paralysis as an inaugurating manifestation of MFS is quite rare and requires special attention from neurologists and otolaryngologists. Although it may present as benign as an acute change in voice, early diagnosis and prompt management may prevent further complications.