Tuberculosis remains a major global health problem, particularly in developing countries. Tuberculous meningitis (TBM) is the most devastating form of extrapulmonary tuberculosis and is associated with significant mortality and long-term neurological disability. Neurological manifestations result from intense meningeal inflammation, vasculitis, hydrocephalus, and cranial nerve involvement occurring predominantly at the base of the brain. Cranial neuropathies develop in approximately 20–50% of patients with TBM and represent an important cause of morbidity [1,2].

Polyneuritis cranialis is characterized by simultaneous involvement of multiple cranial nerves and is uncommon in TBM. The condition may mimic autoimmune, infectious, and neoplastic disorders. Even rarer is the coexistence of TBM with Miller–Fisher syndrome (MFS), a variant of Guillain–Barré syndrome characterized by the triad of ophthalmoplegia, ataxia, and areflexia. MFS is considered an immune-mediated neuropathy frequently triggered by infections and represents approximately 1–7% of Guillain–Barré syndrome cases in Western populations [3,4].

The simultaneous occurrence of TBM, MFS-like manifestations, and renal involvement poses a significant diagnostic challenge. Renal manifestations in tuberculosis may arise due to immune-complex deposition, direct renal involvement, or secondary glomerulonephritis. When neurological and renal abnormalities coexist, clinicians often consider systemic vasculitis, ANCA-associated disorders, or connective tissue diseases before infectious etiologies [5].

We present a series of five patients who demonstrated an unusual overlap syndrome involving TBM, polyneuritis cranialis, Miller–Fisher variant features, and glomerulonephritis. Such presentations remain exceptionally rare and deserve recognition because prompt diagnosis and treatment can significantly improve outcomes [2,6].

Case 1

A 19-year-old male presented with diplopia, headache, unsteady gait, and progressive bilateral ophthalmoplegia for 10 days. Neurological examination revealed sixth and seventh cranial nerve palsies, generalized areflexia, and truncal ataxia. Blood pressure was 190/110 mmHg.

Urinalysis demonstrated microscopic hematuria and proteinuria. CSF analysis revealed lymphocytic pleocytosis, elevated protein (210 mg/dL), and reduced glucose. CSF MTBNAAT detected Mycobacterium tuberculosis. MRI brain demonstrated diffuse leptomeningeal enhancement with a left parietal subcortical lesion.

A diagnosis of TBM with polyneuritis cranialis, MFS overlap, and glomerulonephritis was established. Treatment included antitubercular therapy (ATT), corticosteroids, intravenous immunoglobulin (2 g/kg over 5 days), and antihypertensive therapy. Marked neurological recovery occurred within 8 weeks.

Case 2

A 24-year-old female presented with binocular diplopia, facial weakness, gait instability, and severe headache. Examination revealed bilateral ophthalmoplegia, facial nerve palsy, ataxia, and absent deep tendon reflexes.

Urine examination showed red blood cells and moderate proteinuria. CSF findings were consistent with TBM, and MTBNAAT was positive. MRI demonstrated basal meningeal enhancement and hydrocephalus.

The patient received ATT, dexamethasone, IVIG, and supportive care. At three-month follow-up, ophthalmoplegia had resolved completely and renal parameters normalized.

Case 3

A 28-year-old male was admitted with acute-onset diplopia, dysarthria, dysphagia, and progressive weakness. Neurological examination identified involvement of cranial nerves VI, VII, IX, and X. Areflexia and sensory ataxia were present.

Laboratory investigations demonstrated elevated serum creatinine (1.8 mg/dL), hematuria, and nephritic-range proteinuria. CSF MTBNAAT was positive. MRI revealed extensive leptomeningeal enhancement.

Following ATT, steroids, and IVIG, substantial improvement occurred over 12 weeks.

Case 4

A 17-year-old female presented with fever, headache, visual blurring, and gait imbalance. Examination revealed bilateral abducens nerve palsy, ophthalmoplegia, and generalized areflexia.

CSF analysis demonstrated elevated protein and lymphocytic predominance. MTBNAAT confirmed tuberculosis. Urinalysis showed persistent microscopic hematuria.

Treatment with ATT and IVIG resulted in progressive recovery. Residual mild abduction deficit persisted at six months.

Case 5

A 31-year-old male presented with altered sensorium, diplopia, facial weakness, and severe hypertension. Examination revealed multiple cranial nerve palsies and ataxia.

MRI brain showed diffuse meningeal enhancement and focal ischemic lesions secondary to tuberculous vasculitis. CSF MTBNAAT confirmed TBM. Renal evaluation revealed glomerulonephritis with nephritic syndrome.

Despite aggressive treatment, neurological recovery was incomplete. Persistent facial weakness and gait abnormalities remained at six months.

Table 1. Clinical Characteristics of the Five Cases

Table 2. Radiological and Cerebrospinal Fluid Findings

Table 3. Renal Manifestations

Table 4. Clinical Outcomes

TBM commonly affects the basal meninges, where inflammatory exudates surround cranial nerves and cerebral vessels. This mechanism explains the high frequency of cranial neuropathies observed in advanced disease. Cranial nerve involvement in TBM most frequently affects the second, third, sixth, and seventh cranial nerves [1,2].

The remarkable feature in our series was the simultaneous presence of Miller–Fisher syndrome characteristics. MFS is classically defined by ophthalmoplegia, ataxia, and areflexia and is regarded as an immune-mediated variant of Guillain–Barré syndrome. Anti-ganglioside antibodies, particularly anti-GQ1b antibodies, are frequently implicated in its pathogenesis [3,4,7].

Several infectious agents have been implicated as triggers of MFS, supporting the concept of molecular mimicry. The neurological findings observed in our patients suggest that Mycobacterium tuberculosis may act as a trigger for immune-mediated peripheral nerve dysfunction in susceptible individuals. Similar overlap syndromes involving MFS and other Guillain–Barré variants have been described, although association with TBM remains exceptionally uncommon [8,9].

Renal involvement further complicated diagnosis. Hematuria and proteinuria prompted consideration of systemic vasculitis, lupus nephritis, and ANCA-associated disorders. However, the demonstration of tuberculosis in CSF, together with clinical improvement after antitubercular therapy, supported an infectious rather than primary autoimmune etiology [5,10].

All patients demonstrated characteristic CSF findings of TBM, including elevated protein levels, low glucose concentrations, and lymphocytic predominance. MRI consistently demonstrated leptomeningeal enhancement, reflecting active meningeal inflammation. These findings were congruent with established descriptions of TBM [1,2].

Intravenous immunoglobulin was administered because of prominent MFS-like features and cranial polyneuropathy. Previous studies have shown favorable outcomes in MFS following IVIG therapy, particularly when initiated early [4,7,8].

The favorable outcome observed in four of five patients highlights the importance of prompt diagnosis and multidisciplinary management. Delayed recognition may result in permanent neurological deficits or life-threatening complications. Clinicians should maintain a high index of suspicion for tuberculosis when confronted with concurrent meningeal, cranial nerve, peripheral nerve, and renal manifestations, especially in endemic regions [1,2,5].

This case series describes a rare overlap syndrome involving tuberculous meningitis, polyneuritis cranialis, Miller–Fisher variant of Guillain–Barré syndrome, and glomerulonephritis. The coexistence of central nervous system, peripheral nervous system, and renal involvement may mimic systemic autoimmune disease and delay diagnosis. Recognition of this unusual presentation, confirmation of tuberculosis through CSF molecular testing, and early initiation of antitubercular therapy with immunomodulatory treatment can significantly improve outcomes.

1. Thwaites GE, van Toorn R, Schoeman J. Tuberculous meningitis: more questions, still too few answers. Lancet Neurol. 2013;12(10):999-1010.
2. Wilkinson RJ, Rohlwink U, Misra UK, et al. Tuberculous meningitis. Nat Rev Neurol. 2017;13(10):581-598.
3. Yuki N, Hartung HP. Guillain-Barré syndrome. N Engl J Med. 2012;366(24):2294-2304.
4. Wakerley BR, Uncini A, Yuki N. Guillain-Barré and Miller Fisher syndromes—new diagnostic classification. Nat Rev Neurol. 2014;10(9):537-544.
5. Marais S, Pepper DJ, Marais BJ, Torok ME. HIV-associated tuberculous meningitis—diagnostic and therapeutic challenges. Tuberculosis (Edinb). 2010;90(6):367-374.
6. Eastwood JB, Corbishley CM, Grange JM. Tuberculosis and the kidney. J Am Soc Nephrol. 2001;12(6):1307-1314.
7. Mori M, Kuwabara S, Fukutake T, Hattori T. Clinical features and prognosis of Miller Fisher syndrome. Neurology. 2001;56(8):1104-1106.
8. Martins H, Mendonça J, Paiva D, et al. An overlapping case of Miller Fisher syndrome and the pharyngeal-cervical-brachial variant of Guillain–Barré syndrome. Eur J Case Rep Intern Med. 2020;7(2):001387.
9. Lo YL. Clinical and immunological spectrum of Miller Fisher syndrome. Muscle Nerve. 2007;36(5):615-627.
10. Noioso CM, Napoli A, Bianco A, et al. Miller Fisher syndrome: an updated narrative review. Medicina (Kaunas). 2023;59(8):1520.