Pure Neuritic Leprosy with Bilateral Foot Drop and Central Nervous Involvement: A Clinical, Electrophysiological, and MR Correlation
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.329620
Source of Support: None, Conflict of Interest: None
Keywords: Diffusion tensor imaging, foot drop, mononeuropathy multiplex, nerve biopsy, optic neuritis
The involvement of peripheral nerves in leprosy has been extensively studied, but it is postulated that the bacilli do not invade the central nervous system (CNS) due to its inherent neurotropism for peripheral nerves. Multibacillary leprosy (polar lepromatous, borderline lepromatous, and borderline leprosy) with high bacillary load can involve visceral organs, whereas it is rarely involved in paucibacillary leprosy (polar tuberculoid, borderline tuberculoid, and Asian variant; pure neuritic form)., CNS involvement in leprosy is sparsely reported.,, Limited studies reveal subclinical involvement of optic nerve that varies from 13.5-80% depending on the duration of disease and disease activity., An autopsy report reveals spinal cord degeneration in leprosy secondary to leprous neuropathy., We report three patients of leprosy managed in a tertiary care teaching hospital in eastern India, who presented with bilateral foot drop; spinal cord, cranial nerves II, VIII involvement, and discussed their clinical, radiological, and electrophysiological correlation.
A 17-year-old female presented with asymmetric onset bilateral foot drop of 3 months duration, right foot followed by left. It was associated with bilateral decreased hearing and diminution of vision for 2 months. On examination, she had visual acuity of 6/36 meters, mild-moderate sensorineural hearing loss, power in ankle dorsiflexor was medical research scale (MRC) 2, deep tendon reflexes (DTR) were brisk except diminished ankle jerks, 25% sensory loss in the lateral aspect of both feet, joint position impaired in feet and thickened left common peroneal nerve. Routine blood investigations were normal, cerebrospinal fluid (CSF) total cells 7/cu mm, all mononuclear cells, and normal protein and sugar. Vasculitic profile [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), 24-hour urine protein, antinuclear antigen (ANA)] was normal; Serum vitamin B12 was 336 pg/ml. Nerve conduction studies suggestive of motor-sensory axonal neuropathy in the lower limb [[Table 1] case #1]. Magnetic resonance imaging (MRI) of the dorsal spine revealed dorsal column hyperintensity in the cervicothoracic spinal cord [Figure 1]. Bilateral prolonged visual evoked potential (VEP) (latency P100: right 115, left 120.9 ms), tibial somatosensory evoked potential: normal central sensory conduction. Skin biopsy showed mild perivascular lymphocytic infiltrate in the dermis and no acid-fast bacilli (AFB). Sural nerve biopsy revealed thickening of epineurium and perineurium, endoneurium shows the focal aggregate of lymphocytes and histiocytes, mild axonolysis and demyelination, special stain for AFB reveals bacilli in the cytoplasm of histiocytes and Schwann cells. She was managed with multidrug therapy multibacillary regimen (MDT-MB) with dapsone, clofazimine, rifampicin, and prednisolone 40 mg/day, which was tapered and stopover 2 months, physiotherapy, and foot splint. On 8 months follow-up, there was an improvement in vision, hearing, and ability to walk with minimal assistance. The follow-up MRI showed significant resolution of spinal cord lesion and improvement in P100 latency of VEP [Figure 2].
A 43-year-old lady presented with progressive asymmetrical foot drop of 3 years duration, right followed by left. Examination revealed wasted extensor digitorum brevis (EDB), power of ankle dorsiflexor was MRC grade 2, with normal deep tendon reflexes (DTRs) except decreased ankle jerks and thickened common peroneal nerves. There was 10% sensory loss over the lateral aspect of the sole, joint position sensation was normal. Routine investigations including CSF, vitamin B12, immunological profile were normal. Nerve conduction studies showed axonal changes, normal VEP, and tibial SEP studies. MRI spine and skin biopsy were normal, sural nerve biopsy showed AFB positivity in endoneurium. She was managed with MDT MB regimen and foot drop splint. At 5 months follow-up, she had 1-grade improvement in dorsiflexor of the foot [[Table 1] case# 2].
A 26-year-old female from low socioeconomic status presented with bilateral hearing loss of 13 years duration, asymmetric onset bilateral foot drop for 2 years, and wasting of small muscles of hand for 1 year. Pure tone audiometry examination confirmed moderate sensorineural hearing loss, visual acuity of right eye 3/36, left eye counting finger at 3 meters. EDB and small muscles of hand wasted, dorsiflexor were weak power MRC 2, DTR brisk except diminished ankle reflex. Bilateral ulnar and common peroneal nerves were thickened without tenderness. Routine blood, autoimmune profile and CSF examination were unremarkable. NCS was suggestive of sensory-motor axonal neuropathy, pattern VEP was prolonged bilaterally (P100; Rt-114.3, Lt-119.3 ms). MRI of the spine showed posterior column T2 hyperintensity in the dorsal spinal cord from the D2-D10 level. Skin biopsy was inconclusive, sural nerve biopsy revealed AFB in a special stain. MDT-MB regimen started with steroids in tapering dose. At 6 months follow-up, she showed mild improvement in visual acuity and 1-grade improvement of power in foot dorsiflexor [[Table 1], case# 3].
We describe three cases of pure neuritic form of leprosy who presented with bilateral foot drop and CNS involvement, which was supported by MRI and electrophysiological studies. The prevalence of pure neuritic form of leprosy ranges from 4-8% of all leprosy., The involvement of peripheral nerves in the absence of a predominant cutaneous lesion delays the diagnosis as seen in our cases. Biopsy findings of the affected sensory nerve selected clinically or electrophysiologically confirm the diagnosis. Bilateral foot drop as the initial presentation of leprosy is rare. Choe W first reported unilateral foot drop as an initial presentation in leprosy in a Vietnamese immigrant. Our patients have asymmetric onset bilateral foot drop, mononeuropathy multiplex, thickened nerves, and preserved superficial reflexes that suggested high possibility of leprosy in a setting of leprosy endemic area.
The involvement of the spinal cord and dorsal root ganglionitis is limited to two case reports. Khadilker SV et al. demonstrated that when the patients of leprosy had pan sensory loss with the affection of kinesthetic sensation MRI of the spinal cord may demonstrate the involvement of spinal cord or dorsal root ganglia (DRG). A similar case of leprosy with the involvement of spinal cord DRG was reported recently. Two of our patients also demonstrated spinal cord involvement and MRI showed dorsal column hyperintensity in axial T2W sequence. All these patients had severe impairment of kinesthetic sensation. Diffusion tensor imaging (DTI) of the spinal cord posterior column detects early involvement of cord in sensory neuronopathy as compared to visual T2W hyperintensity of the spinal cord. Fractional anisotropy (FA) value < 0.744 at the level of cervical segment C2-C4 segment has a sensitivity of 0.86 and a specificity of 0.71 in differentiating sensory neuronopathy from a healthy control. Patient #1 and 3 had T2W hyperintensity of cervico dorsal spinal cord and the corresponding lesion showed lower FA and higher ADC value suggestive of loss of white matter fiber tract at dorsal column, which is in concordance with reported autopsy and animal studies., The tibial somatosensory evoked potential (SSEP) showed normal central sensory conduction time with reduced amplitude suggesting axonal loss. The autopsy report of patients of leprosy who were followed for an extended period after treatment revealed degeneration of fasciculus gracilis bilaterally at the dorsal level and lesion extends up to nucleus gracilis. Histopathology demonstrates cellular and fibrillary astrogliosis. The spinal cord involvement in leprosy may be due to the dying back phenomenon following extensive peripheral neuropathy predominantly when large fibers are involved. Direct involvement of the spinal cord shows contrast-enhancing lesion of DRG.,,, In an animal study of the lepromatous mouse model, the organism was detected in the brain parenchyma: gray and white matter, Purkinje cells of the cerebellum and intracranial blood vessels. Spinal cord and anterior horn cells showed leprous bacilli and evidence of neural damage. Transcranial magnetic stimulation of the motor cortex of affected hand muscles due to leprous induced claw hand showed decrease cortical representation as compared to motor cortex representation of normal muscles due to decreased brain plasticity. In a study by Kang et al., normal cognitive function was found despite the worse activity of daily living due to leprosy-induced disability in 224 leprosy patients.
Facial nerve is commonly involved in leprosy. The involvement of optic nerve is rare. In an autopsy study of 50 patients of leprosy, there was no optic nerve or posterior segment eye involvement. In a study of 25 patients of leprosy, the P100 latency (major positive potential) in pattern reversal VEP was prolonged in 80% of patients out of which 11 (85%) patients were tuberculoid leprosy. Two of our patients had diminished vision; pattern VEP shows P100 latency prolongation. Prolongation of VEP suggests the involvement of the optic pathway. Clinical involvement of the optic nerve in leprosy was reported by Moller AR. Van Poole GM et al. described evidence of optic neuritis in 49 (23.8%) cases of leprosy. MRI diffusion parameters of optic nerve help in the diagnosis of subclinical optic neuritis and pattern of involvement whether demyelinating or axonal loss. In a DTI study of 25 patients of previous unilateral optic neuritis using the ZOOM-EPI diffusion sequence/protocol, the FA value was reduced in 35% patients in the affected eye as compared to the healthy control (P < 0.001). The decrease in FA and increase in mean diffusivity in patients of chronic primary angle-closure glaucoma suggest axonal and myelin damage of optic nerve. In our two patients, the clinical findings and prolonged VEP latency suggest demyelinating pathology of the optic nerve. A review of the limited literature and present cases suggest optic pathway involvement in leprosy.
Cases # 1 and 3 had hearing impairment suggestive of sensorineural hearing loss. The study by Kocher et al. demonstrated abnormal brain stem auditory evoked potential in 18 (72%) leprosy patients. They postulated that both peripheral VIII nerve and its central connection is involved more in lepromatous variety and the plausible cause to be central demyelination. In a study of 100 consecutive patients of leprosy, 22 patients had cranial nerve involvement out of which 3 (13.6%) had sensorineural hearing loss and all were in the lepromatous spectrum.
This study highlights that patients of pure neuritic leprosy may manifest with bilateral foot drop with the involvement of posterior column, optic nerve, and cochlear nerve. Further studies with the large sample may give insight into the pathophysiology of CNS involvement in this group of leprosy patients.
We thank Mr. Divendu Deewan for neurophysiological studies and secretarial help. Not the least, we are very thankful to our patients who consented to the research work.
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Conflicts of interest
There are no conflicts of interest.
[Figure 1], [Figure 2]