Acute cerebellar ataxia and peripheral neuropathy due to an atypical infection

Abstract

This 18-year-old boy presented to the hospital with symptoms of cerebellar dysfunction preceded by an acute febrile illness with rash. Examination showed evidence of left-sided cerebellar dysfunction and polyneuropathy. Empirical treatment for leptospirosis and scrub typhus was initiated. MRI was normal. Other organ dysfunctions in the form of thrombocytopenia and transaminitis were also observed. He recovered without sequelae. A diagnosis of acute cerebellar ataxia and polyneuropathy due to scrub typhus was made.

Background

Scrub typhus is a miteborne acute febrile illness mimicking dengue and leptospirosis and is caused by Orientia tsutsugamushi, a gram-negative coccobacillus. O. tsutsugamushi is distributed throughout the Asia-Pacific.¹ In India, it was initially reported in the Himalayan foothills and later began to be described from all areas of the subcontinent.² Neurological manifestations in scrub typhus include meningitis and meningoencephalitis, acute disseminated encephalomyelitis, posterior reversible encephalopathy, cranial nerve palsies, strokes, seizures, cerebellitis, parkinsonism, cortical venous thrombosis, myelitis, plexopathy and polyneuropathy.^{2 3} Isolated cerebellar involvement has been described in eight cases previously, among whom half were adults. A combination of acute cerebellitis with peripheral neuropathy has not been previously reported.

Case presentation

An 18-year-old boy from a neighbouring town presented with low-grade fever of 8-day duration. On the third day of fever, he developed a petechial rash, beginning with the face, rapidly spreading to the trunk and limbs the same day, and disappeared during the next 4 days. From the seventh day of fever, he had difficulty in walking, a feeling of imbalance with a tendency to fall leftwards, dysarthria and vomiting. He visited a nearby hospital, where initial investigations for an acute febrile illness revealed thrombocytopenia and he was referred to our centre on the eighth day.

On examination, he was febrile, with conjunctival suffusion, stable vitals and normal sensorium. He had scanning speech, a broad-based gait with tendency to fall leftwards, left-sided impaired finger nose test and dysdiadochokinesia, and bilateral grade II horizontal nystagmus. Power in the lower limbs were 4+/5 (Medical Research Council) bilaterally, with hyporeflexia and flexor plantars. Upper limb power and reflexes were normal. Graded sensory loss (large and small fibre) was present up to the hip. The rest of the neurological and systemic examination was normal.

Investigations

Laboratory values are given in table 1. On the third day, scrub immunoglobulin M (IgM) was reported positive (ImmuneMed Scrub Typhus Rapid). Lumbar puncture was deferred due to rapid drop in platelet counts (table 1). MRI could be performed only on day 6 of hospitalisation and was reported normal (figure 1A and B). Nerve conduction studies could not be performed due to technical reasons. The febrile panel for chikungunya, dengue, malaria and leptospirosis was negative. HIV testing was non-reactive. The encephalitis panel (herpes simplex virus, scrub typhus and Japanese encephalitis) could not be done since lumbar puncture was not performed.

Table 1.

Timeline of disease progression and investigations during hospital stay

Day of illness	Day 8	Day 9	Day 10	Day 11	Day 12	Day 13	Day 14
Fever	+	+	+	–	–	–	–
Vomiting	+	–	–	–	–	–	–
Conjunctival suffusion	+	+	+	+	Reduced	Reduced further	–
Dysarthria	+	+	+	–	–	–	–
Lower limb power	4+/5 Bilaterally	5/5	5/5	5/5	5/5	5/5	5/5
Swaying	+	+	Improved	Recovered	–	–	–
Nystagmus	Bilateral horizontal gaze	Bilateral horizontal gaze	Bilateral horizontal gaze	On left gaze only	On left gaze only	–	–
Sensory loss in lower limbs bilaterally	Graded, till hip L1–L2	Graded, till hip L1–L2	Graded, till hip L1–L2	Graded, till mid-thigh	Graded, till mid-thigh	Graded, till knee	Graded, till knee
Finger nose impairment	Left side impaired	Left side impaired	–	–	–	–	–
Dysdiadochokinesia	Left side impaired	Left side impaired	–	–	–	–	–
Knee-heel shin test	Left side impaired	Left side impaired	Comparatively better	–	–	–	–
Reflexes	–	–	+/−	+/−	+	+	+
Plantars	Flexors	Flexors	Flexors	Flexors	Flexors	Flexors	Flexors
Investigations
Haemoglobin (g/L)	10	10.6	10.1	11.5	11.1	11.7	11
Total leucocyte count, ×109/L	5.74	4.29	3.47	4.92	6.56	13	13.2
Differential leucocyte count	N87, L10	N85, L11	N50, L34	N56, L38	N35, L48	N34, L55	N39, L53
Platelet counts, ×109/L	91	25	15	8	9	20	32
Urea (mg/dL)	30	34	32	27	25	22	19
Creatinine (mg/dL)	1.1	0.73	0.56	0.57	0.6	0.6	0.6
Albumin (g/dL)	2.9	2.7	2.5	3.1	2.9	3.3	3.5
Total bilirubin (mg/dL)	0.99	0.55	0.63	0.86	0.8	0.8	1.1
Aspartate transaminase (U/L)	187	156	316	588	584	415	284
Alanine transaminase (U/L)	77	78	157	365	499	499	455
Alkaline phosphatase (U/L)	52	51	44	64	68	85	89

Figure 1.

MRI of the cerebrum and the cerebellum, reported to be normal.

Differential diagnosis

An acute febrile illness with cerebellar dysfunction and peripheral sensorimotor neuropathy was considered. Considering his fever, headache, conjunctival suffusion, liver dysfunction, thrombocytopenia and neurological dysfunction, leptospirosis, dengue and scrub typhus were the main differentials.

Treatment

Pending results of the febrile panel, he was empirically initiated on ceftriaxone and oral doxycycline. His clinical progress is described in table 1. Ceftriaxone and acyclovir were discontinued after his scrub IgM result.

Outcome and follow-up

The course was complicated by leucopenia, worsening thrombocytopenia and transaminitis none of which necessitated intervention. He was discharged on day 8, with advice to complete 2-week therapy with doxycycline. Neurological examination and liver function tests were normal when he returned after 10 days. Four months later, on his visit prior to the writing of this report, there was no recurrence of neurological symptoms.

Discussion

Acute cerebellar ataxias in adults are generally due to vascular causes, toxins and drugs, and infections. Cerebellar involvement has been described in many infectious illnesses due to viruses (majority), bacteria and parasites. Atypical infections causing cerebellitis include tuberculosis, malaria, listeria and Lyme disease.⁴ Vascular aetiologies were not considered in our patient due to the fever history, age and normal MRI. History was not suggestive of either a toxin or a drug-related cause.

The most common neurological manifestation in scrub typhus from most case series is meningoencephalitis.³ Cerebellar involvement in scrub typhus has been described in conjunction with other neurological disorders. A diagnosis of cerebellitis may be masked in patients with encephalitis due to an altered mental status. Isolated cerebellar involvement is rare. All the eight cases have been reported from India.^5–12 Four were adults of whom one had an abnormal MRI. In the remaining four children, three had abnormal MRI findings suggestive of cerebellitis.

Acute cerebellitis is usually post-infectious, and associated with fever, altered mental status and abnormal MRI findings, which may have been the case in the three children. Acute cerebellar ataxia is the umbrella term, under which acute cerebellitis is sometimes included, and does not have altered mental status, or MRI evidence of leptomeningeal enhancement or hemispherical changes. In a review of 35 adult cases of acute cerebellitis (MRI proven) between 1991 and 2016, only one case of scrub typhus was seen.¹³

Fourteen cases of isolated peripheral neuropathy have been reported,^14–25 with 10 of Guillain-Barré syndrome (GBS), three of brachial plexopathy^{14 20 21} and one of mononeuritis multiplex¹⁸; five have been reported from India (table 2). Cerebellar involvement and peripheral neuropathy in combination has been reported only in one instance, wherein a 64-year-old man presented with ataxia and sensorimotor neuropathy.²⁵ Multiplication of the rickettsia in the endothelium of capillaries and arterioles, and brain parenchyma, associated with haemorrhages, typhus nodules and demyelination are the pathophysiological basis of neurological involvement in scrub typhus.³

Table 2.

List of reports with cerebellar involvement, neuropathy or both

Isolated cerebellar involvement in scrub typhus
S. no.	Number of cases	Author, country	Year	Comments
1	1	Karanth et al, India5	2013	24-year-old man; first reported case; normal MRI
2	1	Bhat et al, India6	2015	6-year-old female; abnormal MRI
3	1	Mahajan et al, India7	2016	22-year-old woman; abnormal MRI; treated with dexamethasone
4	1	Bhoil et al, India8	2016	21-year-old man; abnormal MRI
5	1	Didel et al, India9	2017	9-year-old male; abnormal MRI
6	1	Ghosh et al, India10	2017	3-year-old female; abnormal MRI
7	1	Gupta et al, India11	2019	26-year-old woman; normal MRI
8	1	Kaiser et al, India12	2020	7-year-old female; normal MRI
Neuropathy
1	1	Ting et al, Taiwan14	1992	Brachial plexus neuropathy
2	1	Le et al, South Korea15	2007	GBS, 42-year-old woman; Rx with IVIG
3	2	Le et al, South Korea16	2009	GBS, 54-year-old man and 74-year-old woman; both Rx with IVIG
4	2	Ju et al, South Korea17	2011	GBS, 46-year-old woman and 50-year-old man; both Rx with IVIG
5	1	Hayakawa et al, Japan18	2012	72-year-old woman with mononeuritis multiplex
7	1	Sawale et al, India19	2014	GBS, 41-year-old man, Rx with PLEX
8	1	Mittal et al, India20	2015	Symmetric brachial plexopathy, 50-year-old man
9	1	Banda et al, India21	2016	Brachial neuritis, 45-year-old woman
10	2	Sakai et al, South Korea22	2016	GBS, 66-year-old woman and 58-year-old man; both Rx with IVIG
11	1	Dev et al, India23	2019	GBS, 20-year-old man; Rx with IVIG
12	1	Juneja et al, India24	2020	GBS, 42-year-old man; Rx with IVIG
Cerebellar involvement with neuropathy
1	1	Kim et al, South Korea25	2008	Cerebellar infarction with polyneuropathy, 64-year-old man

GBS, Guillain-Barré syndrome; IVIG, intravenous immunoglobulin; PLEX, plasma exchange.

There is a paucity of data on the management of neurological manifestations like cerebellar ataxia or peripheral neuropathy. Steroids are recommended if there is cerebellar oedema or hydrocephalus, and hydrocephalus may require surgical intervention.¹³ However, patients diagnosed with GBS are treated with standard care using intravenous immune globulin or plasma exchange.

Patient’s perspective.

It was a harrowing time to see our son unable to walk on his own without swaying. We were at a loss when told that his brain had been affected. Luckily, he improved with treatment, and by the end of 3 weeks, he was back to his usual self.

Learning points.

• Nervous system involvement in scrub typhus is easily treated.

• Isolated acute cerebellar ataxia is an exceedingly rare manifestation of scrub typhus.

• Scrub typhus is ubiquitous, and merits inclusion in the list of atypical infections causing acute cerebellar ataxia.