1. Nervous System Lymphoma n Background u Hodgkin’s disease F Rarely involves the nervous system u Non-Hodgkin’s lymphoma F Involves nervous system in 10% of cases F Less differentiated, diffuse forms and bone marrow involvement increase risk of nervous system spread F Leptomeninges (6-8% of cases) F Epidural space (5% of cases)

2. Neurolymphomatosis n Background u 1907- Marek F Disease of Orpington roosters “Peripheral nerves infiltrated by lymphocytes”“Peripheral nerves infiltrated by lymphocytes” u 1934- Lhermitte and Trelles F “human peripheral neurolymphomatosis” u 1992- Diaz-Arrastia F Reviewed literature on 39 cases

3. Neurolymphomatosis n Background u Rare complication of NHL u At least 50% occur in context of systemic NHL u Most cases are associated with leptomeningeal involvement u Infiltration of spinal nerve roots, dorsal root ganglia and peripheral nerves

4. Neurolymphomatosis n Clinical features u Diaz-Arrastia- 39 cases F Neurology 1992; 42: 1136-1141 u History F Subacute course over weeks most common F Acute/rapid course in ~10% of cases F Pain is common F Ante-mortem diagnosis in 35% of cases

5. Neurolymphomatosis n Clinical Syndrome u Examination F Lower motor neuron syndrome Weakness, sensory loss, areflexiaWeakness, sensory loss, areflexia F Other Cranial neuropathy (18)Cranial neuropathy (18) Bladder or bowel incontinence (10)Bladder or bowel incontinence (10) Ataxia (7)Ataxia (7) Mental changes (5)Mental changes (5)

6. Neurolymphomatosis n Diagnostic tests u CSF F Increased protein (73%) F Lymphocytic pleocytosis (70%) F Positive cytopathology (4/7 assessed) u Electrophysiology F Sensorimotor axonal neuropathy- most common F Mixed axonal/demyelinating neuropathy

7. Neurolymphomatosis u Neuroimaging F Thick, enhancing nerve roots, nerves u Nerve biopsy F Axonal degeneration F Demyelinating F Mixed

8. Neurolymphomatosis n Treatment u Concomitant involvement of subarachnoid space in 2/3 cases at autopsy- need drugs which penetrate blood brain barrier u Anecdotal F Surgery/Biopsy F Radiation F Chemotherapy Systemic plus/minus intrathecalSystemic plus/minus intrathecal

9. Nervous System Lymphoma n Background u CNS Lymphoma (Primary or Secondary) F Brain Most are primaryMost are primary F Leptomeningeal Most are secondaryMost are secondary F Spinal Cord Most secondary, from epidural compressionMost secondary, from epidural compression F Cranial nerve F Intravascular

10. Nervous System Lymphoma n Background u PNS Lymphoma F Nerve root F Plexus F Peripheral Nerve u CNS + PNS F Neurolymphomatosis Relevant to our case reportRelevant to our case report “Symptoms and signs of peripheral neuropathy that are confirmed by histopathologic evidence of lymphomatous infiltration of the nerves as seen by nerve biopsy or autopsy”“Symptoms and signs of peripheral neuropathy that are confirmed by histopathologic evidence of lymphomatous infiltration of the nerves as seen by nerve biopsy or autopsy”

11. Neurolymphomatosis

12. n Differential Diagnosis u Mononeuropathies (nerves, roots, plexuses) F Compression (tumor, vertebral collapse, hematoma) F Pressure palsies (loss of subcutaneous tissue) F Radiation F Herpes zoster F Brachial neuritis

13. Neurolymphomatosis n Differential Diagnosis u Polyradiculoneuropathies F Paraneoplastic (sensory, motor, both) F Guillain-Barre Syndrome F Chemotherapy (Vinca alkaloids) F Nutritional F Herpes zoster F Amyloid