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LETTER TO EDITOR
Year : 2020  |  Volume : 68  |  Issue : 1  |  Page : 222-224

Paraneoplastic Limbic Encephalitis in Hodgkin's Lymphoma Misdiagnosed as Isoniazid Psychosis: A Mystifying Experience


1 Department of Neurology, Baby Memorial Hospital, Kozhikode, Kerala, India
2 Department of Internal Medicine, Baby Memorial Hospital, Kozhikode, Kerala, India

Date of Web Publication28-Feb-2020

Correspondence Address:
Dr. R N Supreeth
Flat No. E8, Crescent Kings Spear Apartment, Mini Bypass Road, Near MIMS Hospital, Calicut . 673 004, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.279695

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How to cite this article:
Kumar V G, Supreeth R N, Pallivalappil B, Raja RS. Paraneoplastic Limbic Encephalitis in Hodgkin's Lymphoma Misdiagnosed as Isoniazid Psychosis: A Mystifying Experience. Neurol India 2020;68:222-4

How to cite this URL:
Kumar V G, Supreeth R N, Pallivalappil B, Raja RS. Paraneoplastic Limbic Encephalitis in Hodgkin's Lymphoma Misdiagnosed as Isoniazid Psychosis: A Mystifying Experience. Neurol India [serial online] 2020 [cited 2020 Apr 7];68:222-4. Available from: http://www.neurologyindia.com/text.asp?2020/68/1/222/279695




Sir,

As per the GLOBOCAN 2012 data, the age-standardised incidence rates of Hodgkin's lymphoma (HL) in India is 5677 per 100,000 population and of non-Hodgkin's lymphoma (NHL) is 15,883 per 100,000.[1] While the incidence of lymphoma is lesser in India when compared to developed countries, the mortality rate is almost equal. This can be ascribed to factors like delayed diagnosis owing to inadequate diagnostic facilities in rural India, affordability issues, incomplete treatment, and poor follow-up.[2] Poor diagnostic facilities often result in misdiagnosis of malignant lymphadenopathy as tubercular lymphadenitis. The picture gets complicated when malignancy presents with atypical manifestations like paraneoplastic neurological syndromes (PNS), as in our patient. With this case report we underline the risk of misdiagnosis by fine-needle aspiration cytology (FNAC), need for improvement in tissue diagnostic facilities in rural India, and importance of repeat neuroimaging at proper intervals to clinch the diagnosis of unusual cases.

A 43-year-old female experienced painless swelling in the left axilla for 1 month. It was diagnosed as tuberculosis (TB) lymphadenitis at a local hospital based on FNAC. She was treated with anti-tubercular therapy (ATT) regimen – isoniazid (INH) 300 mg + rifampicin 450 mg + pyrazinamide 750 mg + ethambutol 800 mg for 10 days. On 11th day of ATT, she developed one episode of generalised tonic-clonic seizures (GTCS) and altered behaviour. Preliminary evaluation at local hospital showed hyponatremia. Two days later she was referred to our center with a suspicion of central nervous system (CNS) TB, hyponatremic seizures and INH psychosis. On arrival, she was conscious but disoriented. Her vitals were normal. An approximately 2 × 3 cm, solitary, soft, mobile, non-tender left axillary lymphadenopathy was noted. Mini-Mental State Examination on 2nd day revealed a score of 14 out of 30. This suggested moderate cognitive impairment. The rest of the neurological examination was normal. Other systems were also unremarkable. Blood cell counts and renal function test were normal. She had transaminitis – AST 512 U/L, ALT 212 U/L and hyponatremia – serum sodium 110 mEq/L. Serum osmolality was 257 mmol/L and urine sodium – 113 mEq/L suggesting syndrome of inappropriate anti-diuretic hormone (SIADH). Ultrasound abdomen and chest X-ray were normal. Cerebrospinal fluid (CSF) cytology, biochemistry and culture studies were normal ruling out CNS TB. Magnetic resonance imaging (MRI) brain showed non-specific white matter hyperintensities [Figure 1]. Our provisional diagnosis was acute symptomatic seizures secondary to hyponatremia, SIADH, TB lymphadenitis and INH psychosis. ATT was stopped in view of psychosis and deranged hepatic function. Fosphenytoin and hypertonic saline were instituted. By Day 5, her psychosis worsened and she experienced one episode of GTCS, despite improvement in serum sodium level (130 mEq/L). This made us re-evaluate her with excision biopsy of involved lymph node. Histopathology showed nodular infiltrates, lacunar Reed–Sternberg (RS) cells and areas of hyalinisation [Figure 2]. Flowcytometry and immunohistochemistry revealed RS cell positivity for CD30 and CD15 markers. This confirmed the diagnosis of HL. However, altered sensorium persisted inspite of corrected metabolic parameters. Hence, MRI brain was repeated on Day 10, which showed bilateral medial temporal lobe and hippocampal hyperintensities on T2-weighted fluid-attenuated inversion recovery (FLAIR) sequence [Figure 3] and [Figure 4]. In the setting of HL, these features suggested paraneoplastic limbic encephalitis (PLE). She was planned for chemotherapy with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) regimen. But the family was not willing for treatment from our center and the case was lost to follow up.
Figure 1: Magnetic resonance imaging brain done on day of admission: Axial section T2-weighted fluid-attenuated inversion recovery sequence showing diffuse non-specific white matter hyperintensities

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Figure 2: Histopathology of excision biopsy specimen showing nodular infiltrates featuring small lymphocytes, histiocytes and plasma cells; uni-, bi- and multinucleate giant cells with prominent nucleoli (red arrow – lacunar Reed–Sternberg cell) and areas of hyalinisation (yellow arrow)

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Figure 3: Magnetic resonance imaging brain done on Day 10: Axial section T2-weighted fluid-attenuated inversion recovery sequence showing bilateral medial temporal lobe hyperintensities (white arrow)

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Figure 4: Magnetic resonance imaging brain done on Day 10: Axial section T2-weighted fluid-attenuated inversion recovery sequence showing bilateral hippocampal hyperintensities (white arrow)

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FNAC is a safe, rapid, cost-effective test with high sensitivity and specificity (88 and 96%, respectively).[3] Polymerase chain reaction (PCR) is expensive and culture studies are time taking. These factors make clinicians largely bank on FNAC to diagnose TB lymphadenitis. However, interpretation of FNAC smear needs proficiency. Correlation of the report with clinical history is also crucial. In a study comparing histopathology reports of FNAC smears with that of excision biopsy specimen, it was established that 20% of the cases with HL were misdiagnosed by FNAC.[4] In a South African study, 18 out of 21 lymphoma cases were misdiagnosed initially as TB.[5] TB being common in tropical countries, generates a general tendency among clinicians to misdiagnose non-tubercular lymphadenopathy as TB lymphadenitis. In our case, clinical worsening despite appropriate management made us reconsider the diagnosis.

INH is known to cause peripheral neuropathy and psychosis. It is believed that INH causes excessive excretion of vitamin B6. This interrupts tryptophan metabolism, required for serotonin synthesis. INH also inhibits pyridoxal-5-phosphate activity in the brain, leading to decreased gamma-aminobutyric acid levels. These effects result in psychosis.[6] INH psychosis can manifest between 1 and 34 weeks after starting the drug.[7] Considering INH psychosis beguiled us from arriving at an early diagnosis. Metabolic derangement also contributed to the delay.

PLE is usually associated with small cell lung cancer and testicular germ cell tumour. HL is the third common cause.[8] It is characterised by amnesia, disorientation, agitation, depression, psychosis and seizures. Diagnosis of limbic encephalitis requires appropriate clinical picture with any one of electroencephalographic, pathological or radiological studies demonstrating temporal lobe abnormalities.[8] A study involving 20 patients of LE demonstrated hyperintensities in unilateral or bilateral medial temporal lobe(s) on T2-weighted FLAIR sequence in all the patients.[9] Our patient satisfied the clinical and radiological criteria for PLE. We could not do antibody testing due to financial constraints. PLE complicating HL usually carries good prognosis. Manifestations subside with successful treatment of HL.

To conclude, diagnosis of TB lymphadenitis should not entirely be based on FNAC. Confirmation with excision biopsy is strongly recommended. Patients referred with a diagnosis of TB lymphadenitis from primary health centres need strong re-consideration of the diagnosis in case of unusual course of events. Cases of HL with altered behaviour require evaluation for limbic encephalitis if they remain symptomatic after treating correctable causes.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgements

We thank Dr. Sharfin Sana Bisma and Dr. Abin Ummer, DNB residents, Department of Radiodiagnosis, Baby Memorial Hospital, for helping us with the interpretation of MRI findings.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013.  Back to cited text no. 1
    
2.
Nair R, Arora N, Mallath MK. Epidemiology of non-Hodgkin's lymphoma in India. Oncology 2016;91(Suppl 1):18-25.  Back to cited text no. 2
    
3.
Chao SS, Loh KS, Tan KK, Chong SM. Tuberculous and nontuberculous cervical lymphadenitis: A clinical review. Otolaryngol Head Neck Surg 2002;126:176-9.  Back to cited text no. 3
    
4.
Sheela KM, Priya MG. Reliability of FNAC as a diagnostic tool in lymphadenopathy. Int J Adv Med 2017;4:1073-7.  Back to cited text no. 4
    
5.
Puvaneswaran B, Shoba B. Misdiagnosis of tuberculosis in patients with lymphoma. S Afr Med J 2012;103:32-3.  Back to cited text no. 5
    
6.
Girling DJ. Adverse effects of antituberculosis drugs. Drugs 1982;23:56-74.  Back to cited text no. 6
    
7.
Jackson SL. Psychosis due to isoniazid. Br Med J 1957;2:743-6.  Back to cited text no. 7
    
8.
Gultekin SH, Rosenfeld MR, Voltz R, Eichen J, Posner JB, Dalmau J. Paraneoplastic limbic encephalitis: Neurological symptoms, immunological findings and tumour association in 50 patients. Brain 2000;123:1481-94.  Back to cited text no. 8
    
9.
Urbach H, Soeder BM, Jeub M, Klockgether T, Meyer B, Bien CG. Serial MRI of limbic encephalitis. Neuroradiology 2006;48:380-6.  Back to cited text no. 9
    


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