Is Perls Prussian Blue Stain for Hemosiderin a Useful Adjunct in the Diagnosis of Vasculitic Neuropathies?

BACKGROUND: Perls Prussian blue stain (PPB) for hemosiderin, a marker of vascular injury is often employed as an adjunct in the diagnosis of vasculitic neuropathies. However, inflammation/vascular injury is also seen in leprosy, immune mediated, paraproteinemic, diabetic neuropathies, etc. The frequency of detection of hemosiderin in these neuropathies and its utility in diagnosis of vasculitis has not been explored. OBJECTIVE: We evaluated 208 peripheral nerve biopsies for hemosiderin deposits by PPB stain in vasculitis (78) and compared with inflammatory/immune neuropathies [leprous neuritis-32, chronic inflammatory demyelinating polyneuropathy (CIDP)-15, paraproteinemic neuropathies (POEMS)-12, diabetic neuropathy-37] and nonimmune neuropathies [Charcot-Marie-Tooth (CMT) disease-15, vitamin B12 deficiency-7, and ischemic neuropathy in aged-12)]. RESULTS: Hemosiderin deposits were most frequent in vasculitis (48.72%) [59.2% in systemic; 43.1% in nonsystemic vasculitides] and enhanced the sensitivity of diagnosis in "probable" vasculitis (34.48%) that lacked transmural inflammation. Hemosiderin was also detected in infectious/immune-mediated neuropathies (leprous neuritis-56%, POEMS-33.3%, diabetes-18.9%) but absent in CMT, B12 deficiency, and ischemic neuropathy. Hemosiderin deposits involved epineurium in vasculitis, compared to endoneurial/perineurial location in leprosy and perineurial in POEMS and diabetic neuropathy. The sensitivity of detection was high in vasculitic neuropathy (49.35%) compared to other inflammatory neuropathies (22.3%) (P < 0.05) with high specificity (77.69% [positive predictive value (PPV)-56.71%; negative predictive value (NPV)-71.6%]. The specificity increased to 89% if leprous neuropathy was excluded, with PPV-77.5% while NPV dropped to 68.5%. CONCLUSION: These findings suggest that PPB stain for detection of hemosiderin is a useful adjunct in diagnosis of vasculitic neuropathy with high specificity but low sensitivity.

Tangier's disease: An uncommon cause of facial weakness and non-length dependent demyelinating neuropathy.

Tangier disease is an autosomal recessive disorder characterized by an abnormal accumulation of cholesterol esters in various organs secondary to adenotriphosphate binding cassette transporter A-1 (ABCA-1) transporter deficiency and disrupted reverse cholesterol transport. It causes neuropathy in half of the affected individuals. We present the clinical, electrophysiological, and histopathological findings in a middle aged gentleman of Tangier disease who was initially misdiagnosed leprosy and treated with antileprosy drugs. The presence of a demyelinating neuropathy on electrophysiology in a patient with predominant upper limb involvement and facial diplegia should raise the suspicion of Tangier disease. The characteristic lipid profile of Tangier disease was noted in this patient viz. extremely low high density lipoprotein (HDL), elevated triglyceride (TG), and reduced apolipoprotein A1. Estimation of serum lipids should form a part of routine evaluation in order to avoid misdiagnosis.

An uncommon cause of bifacial weakness and non-length-dependent demyelinating neuropathy.

Tangier disease is a rare metabolic disorder that causes neuropathy in half of the affected individuals. We present the clinical, electrophysiological, and histopathological findings in a middle-aged gentleman of Tangier disease who was initially diagnosed as leprosy and treated with antileprosy drugs. The presence of a demyelinating electrophysiology in a patient with predominant upper limb involvement and facial diplegia should raise the suspicion of Tangier disease. Estimation of serum lipids should form a part of routine evaluation in order to avoid misdiagnosis.

Neuropathy in elderly: lessons learnt from nerve biopsy.

OBJECTIVE: To study the utility of nerve biopsy in providing diagnostic, therapeutic or prognostic information that aid in clinical management in elderly subjects with peripheral neuropathy. METHODS: Clinico-pathological data of 100 elderly subjects aged 65 and above with peripheral neuropathy who underwent nerve biopsy in the last decade (2002-2011) was reviewed. RESULTS: The study included 100 subjects (M:F 78:22). Mean age at biopsy and symptom duration was 69.62±4.8 years and 24.17±40.4 months, respectively. The most common pattern of was distal symmetric sensorimotor polyneuropathy (35%), followed by multiple mononeuropathy (29%) and asymmetric sensorimotor neuropathy (15%). The nerve biopsy was 'diagnostic' in 24%, (definite vasculitis in 12, leprosy in 10 and acute inflammatory demyelinating polyradiculoneuropathy in 2) and proved 'essential' or 'helpful' in therapeutic management in 81% subjects. In 60 (60%) patients, where a pre-biopsy aetiological diagnosis could be arrived at based on the available data, nerve biopsy confirmed the diagnosis in 29 of 60 (48.3%), and offered a new diagnosis in 25 (41.7%). A higher yield of biopsy was noted in subjects with asymmetric/multiple mononeuropathy compared with symmetric neuropathies (32.7% versus 17.7%). In 40 (40%) patients without a pre-biopsy aetiological diagnosis, nerve biopsy was 'essential' in 7 of 40 (17.5%) as it provided a definitive diagnosis (definite vasculitis: 5, leprosy: 2), and 'helpful' in 21 of 40 (52.5%) (ischaemic neuropathy: 10, possible vasculitis: 9, probable vasculitis: 2). CONCLUSION: Nerve biopsy aided in the detection of potentially treatable disorders and influenced patient management in a significant proportion of elderly subjects with peripheral neuropathy (81%), particularly in subset with undiagnosed neuropathies confirming that it's a useful tool in diagnosis of neuropathy in the elderly. With minor differences, the aetiological profile in our biopsied neuropathic elderly subjects may reflect the findings in other similar cohorts.