A Woman With Difficulty Walking and Ataxia

A 67-year-old woman complained of weakness in both lower extremities for 3 months; she also had burning sensations in her feet and difficulty walking, with marked unsteadiness which caused her to fall and fracture her right ankle.

Previous studies that were reviewed included normal MRIs of the brain, neck, and lumbosacral spine. Cerebrospinal fluid abnormalities consisted of elevated glucose of 82 mg/dL (normal, 40–60 mg/dL) and protein of 126 mg/dL (normal, 20–40 mg/dL); there were no cells.

Past medical history was positive for hysterectomy, cholecystectomy, pulmonary fibrosis, and carcinoma of the right breast, treated only with mastectomy 10 years before.

Family and social history were noncontributory.

Neurologic examination revealed normal higher cortical functions and cranial nerves. There was mild weakness in the hands and intrinsic muscles of the feet. All deep tendon reflexes were absent. She had decreased vibration sense in the toes, ankles, knees, and fingers, decreased position sense in the toes, ankles, and fingers, and decreased two-point discrimination in fingers and toes. There were pain and touch sensory deficits to 5 cm above the ankles. Finger-to-nose and heel-to-shin testing were fairly well done but were very abnormal when performed with her eyes closed. Romberg’s test was positive, and she had an ataxic gait. She had no Babinski signs.

What is the Differential Diagnosis?

This patient presented with an unsteady gait and progressive sensory ataxia with significant proprioceptive deficits and minimal weakness, indicating an ataxic sensory neuropathy. The slow progression of symptoms is against the sensory ataxic variant of Guillain–Barré syndrome, but the presentation is compatible with chronic sensory inflammatory demyelinating polyneuropathy. A sensory neuropathy associated with Sjögren syndrome is an important consideration, as in this condition there is an ataxic sensory neuronopathy caused by degeneration of the posterior root ganglia neurons with inflammation, but she had no symptoms of this disease. Table 69-1 lists the differential diagnosis of ganglionopathies.

Table 69-1

Differential Diagnosis of Sensory Polyradiculopathy/Polyganglionopathy/Polyganglioradiculoneuropathy

Reproduced with permission from Smith BE, Windebank A, Dyck PJ. Nonmalignant inflammatory sensory polyganglionopathy. In: Dyck PJ, Thomas P, eds. Peripheral Neuropathy . Vol. 2. 4th ed. Philadelphia, PA: Elsevier Saunders; 2005:2315.

Sensory Polyradiculopathy/Polyganglionopathy/Polyganglioradiculoneuropathy	History	Physical Findings	Laboratory Abnormalities
MISP	Smoking history, weight loss, may have autonomic/CNS symptoms	Distal and proximal upper and lower limb symmetrical or asymmetrical hypesthesia, loss of deep tendon reflexes, normal strength, sensory ataxia, pseudoathetosis	Antineuronal nuclear antibodies, abnormal chest imaging; low-amplitude SNAPs; autonomic testing abnormalities
NISP, idiopathic	Hyperacute, acute, subacute, or chronic presentations	Distal and proximal upper and lower limb symmetrical or asymmetrical hypesthesia, loss of deep tendon reflexes, normal strength, sensory ataxia, pseudoathetosis	No distinctive features; low-amplitude SNAPs (must aggressively exclude serologic and imaging evidence of occult malignancy)
NISP, Sjögren-associated	Xerophthalmia, xerostomia	Distal and proximal upper and lower limb symmetrical or asymmetrical hypesthesia, loss of deep tendon reflexes, normal strength, sensory ataxia, pseudoathetosis	Elevated extractable nuclear antigen antibodies; positive Schirmer test; minor salivary gland inflammation; low-amplitude SNAPs
Toxic sensory polyganglionopathy Pyridoxin Cisplatin Paclitaxel Semisynthetic penicillins	Relevant exposure	Distal and proximal upper and lower limb symmetrical or asymmetrical hypoesthesia, loss of deep tendon reflexes, normal strength, sensory ataxia, pseudoathetosis	Normal CSF protein; low-amplitude SNAPs
Acute inflammatory demyelinating polyradiculoneuropathy (sensory variant)	Acute or subacute onset; ± antecedent febrile illness	Distal > proximal ascending findings, typically symmetrical	CSF albuminocytologic dissociation; nerve conductions suggesting demyelination; low-amplitude SNAPs
Chronic inflammatory demyelinating polyradiculoneuropathy (sensory variant)	Chronic progressive course	Distal > proximal deficits, typically symmetrical	CSF cytoalbuminologic dissociation; nerve conductions suggesting demyelination; low-amplitude SNAPs
IgM paraproteinemic neuropathy	Chronic progressive course	Distal > proximal deficits, typically symmetrical, sensory ataxia	IgM monoclonal paraproteinemia; low-amplitude SNAPs

CNS , Central nervous system; CSF , cerebrospinal fluid; IgM , immunoglobulin M; MISP , malignant inflammatory sensory polyganglionopathy; NISP , nonmalignant inflammatory sensory polyganglionopathy.

Diabetic neuropathy can present with sensory ataxia and proprioceptive deficits, but this usually is seen in patients with a long-standing history of the disease, and this patient was not a diabetic.

She did not receive chemotherapy for her breast cancer nor did she take excessive pyridoxine, both of which can cause a sensory neuropathy. That this patient had cancer could suggest autoimmune paraneoplastic neuronopathy, which is usually associated with small cell carcinoma of the lung.

The possibility of combined degeneration of the spinal cord also had to be considered. The absence of Babinski signs or other evidence of spinal cord involvement, however, is against this diagnosis. B ₁₂ deficiency, on the other hand, might rarely manifest only with a peripheral neuropathy. There were no pupillary abnormalities to suggest tabes dorsalis. The lack of sphincter problems and long tract signs is against a myelopathy, and she had a normal MRI of the neck.

An EMG Test was Performed

Motor Nerve Studies

Nerve and Site	Latency (ms)	Amplitude (mV)	Conduction Velocity (m/s)
Peroneal Nerve R.	Normal ≤ 5.7	Normal ≥ 3	Normal ≥ 40
Ankle	4.2	4	–
Fibular head	12.0	4	44
Knee	14.0	4	50

Tibial Nerve L.	Normal ≤ 5.3	Normal ≥ 4	Normal ≥ 40
Ankle	5.0	9	–
Pop. fossa	14.9	7	41

Median Nerve R.	Normal ≤ 4.2	Normal ≥ 6	Normal ≥ 50
Wrist	3.8	8	–
Elbow	7.7	7	53

Nerve and Site	Latency (ms)	Amplitude (mV)	Conduction Velocity (m/s)
Ulnar Nerve R.	Normal ≤ 3.6	Normal ≥ 8	Normal ≥ 50
Wrist	2.8	13	–
Below elbow	6.6	11	53
Above elbow	8.8	10	55

F-Wave and Tibial H-Reflex Studies

Nerve	Latency (ms)	Normal Latency ≤ (ms)
Peroneal nerve R.	52.5	54
Tibial nerve L.	53.9	54
Median nerve R.	28.3	30
Ulnar nerve R.	28.6	30
H-reflex R.	NR	34
H-reflex L.	NR	34

Sensory Nerve Studies

Nerve	Onset Latency (ms)	Normal Onset Latency ≤ (ms)	Peak Latency (ms)	Normal Peak Latency ≤ (ms)	Amp (μV)	Normal Amp ≥ (μV)	Conduction Velocity (m/s)	Normal Conduction Velocity ≥ (m/s)
Sural nerve R.	NR	3.5	NR	4.0	NR	11	NR	40
Superficial peroneal nerve R.	NR	3.5	NR	4.0	NR	8–10	NR	40
Ulnar nerve R.	2.6	2.6	3.1	3.1	2	13	50	50
Median nerve R.	2.8	2.6	3.3	3.1	4	20	46	50