Peripheral Neuropathy in Brucellosis.

Anirudh Anilkumar, Atul Kakkar, Atul Gogia.

Abstract:

Brucellosis is an endemic bacterial infection in the Indian subcontinent, which is seldom

reported to present with peripheral neuropathy. This case involved a 62 year old female
patient. She complained of intermittent fever, associated with arthralgia. Blood tests against
scrub typhus, leptospira, brucella, dengue, and RT PCR for SARS CoV-2 were all negative.
In view of PUO, a PET scan was done which was suggestive of inflammatory aetiology
involving both sacroiliac joints. She was discharged, and prescribed doxycycline,
acetaminophen, and multivitamins. Due to persistent fever, a repeat Brucella antibody panel
was done two weeks after discharge, which showed a rising titre (1:80 - Brucella melitensis
and 1:160 - Brucella abortus) following which the patient was started on streptomycin
injections as well. A follow up test showed a reduced titre (1:80 - Brucella abortus and <1:40
- Brucella mellitensis.) Two weeks following the test, the patient reported to the hospital
complaining of difficulty in walking and numbness of limbs. Video nystagmography was done
to rule out vestibular causes of imbalance such as due to aminoglycoside toxicity, and nerve
conduction studies were performed which showed mild, distal, symmetrical, large fiber,
sensory polyneuropathy involving bilateral upper limbs. A diagnosis of Brucellosis associated
peripheral neuropathy was made, and repeat Brucella antibodies were negative. The patient
was discharged following improvement in mobility.

1. Introduction:

Brucellosis is a bacterial disease with a wide array of non-specific, multisystem symptoms

that generally occur within 14 days but sometimes up to 90 days after inoculation. The
common presentations are fever (78%), arthralgias (65%), back pain (45%), gastrointestinal
symptoms (26%), hepatomegaly (23%), and splenomegaly (26%) [1]
Peripheral neuropathy is rarely reported in Brucellosis because it is often subclinical and
presents later than the aforementioned presentations. It is estimated that upto 18% of
patients with Brucellosis can have subclinical peripheral neuropathy. [2]
This paper reports a case of human brucellosis involving symptomatic peripheral neuropathy
at a tertiary care hospital in India.

2. Case Report:
A 62 year old female patient, who is a retiree, complained of intermittent fever associated
with bilateral knee joint pain for a month. She was also diagnosed with hypertension 12
years back which she is on medication for. Examination did not reveal any organomegaly or
specific signs. Blood tests against scrub typhus, leptospirosis, brucellosis, dengue, and RT
PCR for SARS CoV-2 were all negative. In view of pyrexia of unknown origin, a PET scan
was done which showed mildly FDG avid diffuse periarticular sclerosis around bilateral
sacroiliac joints and bilateral knee joints, suggestive of inflammatory aetiology. ANA profile,
ANA (IF) and ANCA panel, were all negative. She was discharged, and prescribed
doxycycline, acetaminophen, and multivitamins. Due to persistent fever, a repeat Brucella
antibody panel was done two weeks after discharge, which showed a rising titre (1:80 -
Brucella melitensis and 1:160 - Brucella abortus) following which the patient was started on
streptomycin injections in addition to the oral doxycycline regimen. A follow up test showed a
reduced titre (1:80 - Brucella abortus and <1:40 - Brucella mellitensis.)

Two weeks following the test, the patient reported to the hospital complaining of difficulty in
walking, which was insidious in onset and progressive, as well as numbness in her limbs.
The patient was initially able to walk with a stick, and then unable to walk without a helper’s
support. Video nystagmography was performed to rule out vestibular causes of imbalance
due to aminoglycoside toxicity, and a nerve conduction velocity study was performed which
showed mild, distal, symmetrical, large fiber, sensory polyneuropathy involving bilateral
upper limbs. Electromyography showed chronic neurogenic changes in the distal muscles of
both upper and lower limbs with no active denervation. Liver and renal function tests were all
normal. A diagnosis of Brucellosis associated peripheral neuropathy was made and repeat
Brucella antibodies were negative. Patient was advised to continue the full course of the
antibiotics, and was discharged with some improvement in mobility.

Table 1: Results of Brucella antibody titres prior to, during, and post-treatment.

Phase Results Description

Pre-treatment (26/08/2020 +++ Brucella abortus 1:160 and Brucella melitensis 1:80

During treatment ++ Brucella abortus 1:80 and Brucella melitensis < 1:40
(25/09/2020/)

Post treatment (10/10/2020) - Brucella abortus <1:40 and Brucella melitensis < 1:40
 Table 2: Prevalence of common presentations of Brucellosis as per various studies. [3]

Study No. of Fever or Arthralgia or Hepatomegaly Splenomegaly

Patients Chills Arthritis
Memish et al 160 146 (91.3%) 105 (65.6%) 9 (5.6%) 11 (6.9%)
(2000) [13]
Kokoglu et al 138 108 (78.3%) 107 (77.5%) 37 (26.8%) 50 (36.2%)
(2006) [14]
Mantur et al 495 417 (84.2%) 117 (23.6%) 56 (11.3%) 95 (19.2%)
(2006) [15]
Ruiz-Mesa et 711 702 (98.7%) 353 (49.6%) 250 (35.2%) 148 (20.8%)
al (2005) [16]
Barroso 565 441 (78.1%) 248 (43.9%) 422 (74.7%) 152 (26.9%)
Garcia et al
(2002) [17]
Hasanjani 469 314 (67%) 252 (53.7%) ... 27 (5.8%)
Roushan et
al (2004) [18]
Pappas et al 100 91 (91%) 44 (44%) 7 (7%) 16 (16%)
(2005) [19]
Troy et al 28 25 (89%) 15 (54%) 8 (29%) 5 (18%)
(2005) [20]
Andriopoulos 144 144 (100%) 125 (86.8%) ... 74 (51.4%)
et al
(2007) [21]
Giannakopo 52 42 (81%) 43 (83%) ... ...
ulos et al
(2006) [22]
Mantur et al 93 49 (53%) 19 (20%) ... ...
(2004) [23]
Tsolia et al 39 27 (69%) 27 (69%) 11 (28%) 15 (38%)
(2002) [24]

3. Discussion:

Human brucellosis is not an uncommon infection in the Indian subcontinent, however the
peripheral neuropathy seen in cases, is usually sub clinical. [2] Apart from the sub clinical
aspect of peripheral neuropathy as a presentation in human Brucellosis, there is a paucity of
data available regarding its onset and prevalence.

Additionally, features considered to be classical such as hepatosplenomegaly and

splenomegaly were absent in this case.

References:

1. Anna S Dean, Lisa Crump, Helena Greter, Jan Hattendorf, Esther Schelling, Jakob
Zinsstag (2012) Clinical Manifestations of Human Brucellosis: A Systematic Review and
Meta-Analysis. PLoS Negl Trop Dis. 2012 Dec; 6(12): e1929 [PubMed]
2. Sanivar H, Kose Ozlece H, Huseyinoglu N, Aydin E, Ilik F (2017) Frequency of subclinical
peripheral neuropathy in cases of untreated brucellosis. J Infect Dev Ctries 11:753-758. doi:
10.3855/jidc.8056
3. Medscape Article.