A good guideline is only to biopsy a clinically affected sensory nerve with an absent or severely reduced sensory action potential. dysphagia, ophthalmoparesis and severely poor and wasted legs. Symptoms began aged 20 with electric-shock pains and paraesthesia in both feet progressing to the lower calves over 6 months. He then developed buttock numbness and occasional GADD45B faecal incontinence. By age 22, he had diffuse lower limb weakness and wasting, with difficulty standing Folic acid from a seated position and frequent tripping. He became wheelchair dependent within 3 years. Over the same time period he developed progressive facial weakness, bilateral ptosis, slurred speech, difficulty chewing and swallowing, and lost 10kg of weight. He complained of hearing difficulty, and an audiogram exhibited high frequency hearing loss. Important negatives included absence of upper limb symptoms, autonomic, cardiac, respiratory or cognitive dysfunction. He was from a non-consanguineous, Lithuanian background and the eldest of 3 siblings. He was born following a normal pregnancy and delivery, and motor development was normal. He had a left corneal abrasion with visual impairment following an accidental chemical injury aged 14. During the initial investigation of his symptoms (age 23), a choroid plexus lesion in the fourth ventricle was found. It was completely resected and histology confirmed benign choroid plexus papilloma (CPP), WHO grade I. Post-operative neuro-oncology discussion deemed the lesion cured. Examination He had bilateral ptosis, bilateral facial wasting, and could not close his mouth against gravity (Physique 1a). Visual acuity was reduced to belief of light on the left, 6/9 on the right. There was almost complete, complex ophthalmoplegia (Physique 1b) without fatigueability. Trigeminal sensation was reduced. He could not achieve eyelid Folic acid closure; frontalis, buccinator and orbicularis oris were symmetrically poor. Speech was dysarthric and tongue was poor. Uvula was central with symmetrical palatal movement, but gag reflex was reduced. Open in a separate window Physique 1 Clinical examination at age 26.Photographs provided by the patient demonstrate degree of facial (a) and lower limb (b) wasting. Diagramatic representation of ophthalmoparesis is usually shown in (c). Tone, power, muscle bulk, reflexes and sensation were normal in the upper limbs. There was marked wasting of lower limb muscles with flat feet (Physique 1b) and global, slightly asymmetrical weakness with 3/5 hip flexion power bilaterally compared to 4- in extension, knee flexion 4- bilaterally, knee extension 4 on the right, 4+ left, ankle dorsiflexion 0 on the right, 3 left, and plantar flexion 4 bilaterally. Tone was normal and reflexes were absent with flexor plantars. He could just stand from the chair with assistance and take a few impartial actions with trendelenberg gait and foot drop. He had reduced pinprick sensation to mid-shin on the right, ankle on the left. Vibration was reduced to the costal margins; joint position absent at the hips. Q1 How would you anatomically localise the pathology and what would be the most helpful first test? Complex ophthalmoplegia can be due to ocular myopathy, myasthenia, multiple cranial neuropathies or brainstem disease affecting conjugation pathways. Facial weakness Folic acid (involving frontalis) with wasting implies lower motor neuron pathology. Sensory deficit involving of cranial nerves CNV and VII excludes myopathic and neuromuscular junction disorders so the pathology must involve multiple cranial nerves. The pattern of sensory disturbance and weakness in the lower limbs designed in a non-length dependent fashion, affecting the dorsum of the feet and anterior shins (L4/5) and buttocks (S3/4) sequentially. Weakness and sensory loss to above the knees without upper limb involvement is usually incompatible with a length-dependant peripheral neuropathy and suggests polyradiculopathy. Neurophysiology including nerve conduction studies (NCS) and electromyogram (EMG) would be the initial investigation of choice (Table 1). Table 1 Folic acid Nerve conduction studies and EMG preformed age 26. or em SCL52A3 /em )Meningitic infiltration- Lymphoma, TB, basal skull granulomatosis, sarcoidosis, bechetsFacial Onset Sensory Motor Neuronopathy (associated with em TDP43 /em )AL amyloidosisTangiers ( em ABCA1 /em )Sjogrens Open in a separate windows Q4 What would you do next? On the basis of this differential diagnosis a number of blood assessments were performed. FBC, ESR, CRP, liver function and renal profile were normal; CK=219 IU. B12 and folate were normal; plasma homocysteine= 13.9 umol/L (5-12), Methylmalonate = 0.12 umol/L (0-0.28). Rheumatologic /vasculitic screen were normal or unfavorable. Infection screen including HIV, lyme, hepatitis and syphilis serology were unfavorable. TB culture was unfavorable on blood and CSF. AChR, MuSK, Ganglioside and antineuronal.