Autoimmune and Cancerous Brain Conditions Causing These Symptoms
The symptom pattern described—tingling in lower legs/feet, heavy walking sensation, and burning in both arms—is not typical of primary brain pathology but rather suggests peripheral nervous system involvement, which can occur with paraneoplastic syndromes or systemic autoimmune conditions that secondarily affect the brain.
Primary Differential: Peripheral Neuropathy with Potential CNS Involvement
The clinical presentation follows a classic length-dependent sensory polyneuropathy pattern with distal lower extremity symptoms (tingling, heaviness) and upper extremity involvement (burning), suggesting peripheral nerve pathology rather than isolated brain disease 1.
Paraneoplastic Syndromes (Cancer-Related)
Most relevant cancer-associated conditions include:
Small cell lung cancer, thymic neoplasm, breast cancer, ovarian teratoma, testicular tumors, neuroblastoma, and lymphoma are the most common malignancies causing paraneoplastic neurological syndromes that can affect both peripheral and central nervous systems 1.
Paraneoplastic peripheral neuropathy typically presents as sensory or sensorimotor polyneuropathy with numbness, tingling, and pain in a stocking-glove distribution, beginning distally in fingers and toes 1.
Cancer screening with CT chest/abdomen/pelvis is essential at initial presentation, as the neurological symptoms may precede cancer diagnosis 1.
Autoimmune Conditions Affecting Brain and Peripheral Nerves
Autoimmune encephalitis with peripheral involvement:
Autoimmune encephalitis can present with multifocal neurological symptoms including both CNS and peripheral nervous system manifestations 1, 2.
Brain MRI with T1, T2, and FLAIR sequences is essential to evaluate for CNS vasculitis or inflammatory changes 1.
CSF analysis should include cell count, protein, glucose, IgG index, oligoclonal bands, and neural autoantibody panels 1.
HCV-related autoimmune manifestations:
Hepatitis C can cause both peripheral neuropathy and CNS involvement through immune-mediated mechanisms, presenting with distal symmetric sensory/sensorimotor polyneuropathy with paresthesias, numbness, burning feet, and tingling 1.
CNS involvement may present with fatigue, cognitive impairment, or stroke episodes due to vasculitic/vasculopathic changes 1.
Electromyography with nerve conduction studies and brain MRI are indicated for suspected cases 1.
POEMS syndrome:
This rare plasma cell disorder causes polyneuropathy, organomegaly, endocrinopathy, M proteins, and skin changes with progressive weakness and tingling/burning in extremities 3.
Presents with demyelinating polyneuropathy (typically λ-restricted monoclonal protein) and systemic manifestations 3.
Conditions Affecting Both CNS and PNS Simultaneously
Combined central and peripheral demyelination:
Autoimmune demyelinating diseases can affect both CNS and PNS either sequentially or simultaneously, though this is considerably rarer than isolated MS or CIDP 4.
These may be caused by common autoimmune reactivity against myelin antigens present in both nervous systems 4.
Critical Diagnostic Workup
Immediate investigations required:
Brain MRI with contrast (T1, T2, FLAIR, DWI sequences) to evaluate for inflammatory, ischemic, or neoplastic lesions 1.
Lumbar puncture with comprehensive CSF analysis including cell count, protein, IgG index, oligoclonal bands, and neural autoantibody panel 1.
Cancer screening with CT chest/abdomen/pelvis in adults, with additional mammography in women and testicular ultrasound in men 1.
Electromyography and nerve conduction studies to characterize peripheral neuropathy pattern 1.
Serum testing for neural autoantibodies, paraneoplastic antibodies, HCV, vitamin B12, thyroid function, and monoclonal proteins 1, 3.
Important Clinical Pitfalls
Do not assume brain pathology based on these symptoms alone—the distribution pattern (distal lower extremities progressing to upper extremities) is characteristic of peripheral neuropathy, not primary brain disease 1.
Consider toxic/metabolic causes including chemotherapy exposure (if applicable), diabetes, vitamin deficiencies, and other systemic conditions that can mimic autoimmune or paraneoplastic syndromes 1.
Urgent evaluation is warranted because paraneoplastic syndromes may precede cancer diagnosis by months, and early cancer detection significantly impacts outcomes 1.