Hypomagnesemia: A Rare Cause of Movement Disorders, Myopathy and Vertical Nystagmus

The incidence of hypomagnesemia has been reported as 12% among hospital admissions but hypomagnesemia is frequently underdiagnosed. ¹ Neurological symptoms include nausea, headache, vertigo, cognitive impairment, neuronal hyperexcitability, cerebellar and eye signs. ² , ³ We report a patient with hypomagnesemia presenting with ataxia, tremors, myoclonus, downbeat nystagmus (DBN) and proximal myopathy.

Case Report

A 62 year old man with one month history of episodic vertigo and walking imbalance, upper limb jerks and intermittent oscillopsia without diplopia, associated with transient confusion, presented with acute onset of painless lower limb proximal weakness that was rapidly progressing for three days. He was diabetic and on proton pump inhibitors (PPI) for many years.

Mental status examination was normal. Examination showed intermittent DBN in primary gaze with torsional component (Video 1). It was associated with DBN in lateral gaze, hypermetric saccades and broken pursuits. Chvostek sign, myoclonic jerks involving the face and upper limbs were present, in addition to coarse postural jerky tremors in upper limbs (Video 1). Muscle wasting was observed over forearm, quadriceps and distal extremities. Power examination showed iliopsoas and gluteus – 2/5, quadriceps and hamstrings – 4/5 with normal power in other muscle groups. Reflexes in upper limbs were brisk and plantar responses were flexor. Tandem gait was impaired.

Video 1.

Shows vertical nystagmus with downbeat and torsional component (segment 1), coarse postural tremors of the upper limb (segment 2), myoclonic jerks of both upper limbs (segment 3).

Blood investigations revealed elevated creatine phosphokinase (CPK) (5163 u/L), hypocalcemia (7.1 mg/dl) (Table 1). MRI brain was normal. He was started on high dose oral calcium with which serum calcium failed to rise and the symptoms persisted. Serum magnesium level was low (0.9 mg/dl). Urine magnesium levels were also low. A diagnosis of hypomagnesemia secondary to chronic PPI consumption was considered.

TABLE 1.

List of Investigations and the Results

Investigations	Results
Hemoglobin	10.5 gm/dl
Total leucocyte count	14,000 cells/cumm
Serum albumin	2.6 gm/dl
Creatine Phosphokinase	5163 u/l
Serum calcium	7.1 mg/dl
Serum magnesium	0.9 mg/dl; normal range – 1.6 mg–2.3 mg/dl
Parathyroid hormone	9.7 pg/ml; normal range – 15–65
Renal function test	normal
Vitamin B12	normal
Thyroid profile	normal
Anti TPO	12 IU/ml (normal)
HIV	Negative
VDRL	Negative
ANA, ANA profile	Negative
ANCA	Negative
Anti NMDA	Negative
Anti VGKC	Negative
Anti LGI	Negative
Anti‐amphiphysin	Negative
Anti‐CV2	Negative
Anti‐PNMA2	Negative
Anti‐Ri	Negative
Anti‐Yo	Negative
Anti‐Hu	Negative
Anti‐recoverin	Negative
Anti‐SOX1	Negative
Anti‐Titin	Negative
Anti‐GAD	Negative
MRI brain	Normal
PET CT whole body	Negative

He was started on intravenous magnesium infusion, 4–6 gm per day and underwent magnesium monitoring twice daily based on which further titration of magnesium replacement was made, subsequently maintained with oral magnesium. Serum calcium and CPK levels normalized. Clinical improvement took place over 5 days. Apart from subtle gaze evoked nystagmus (Video 2), his DBN, myoclonus and ataxia improved completely at discharge. Tremors improved partially. His power at hip‐iliopsoas/gluteus improved to 4/5.

Video 2.

Fine gaze evoked nystagmus after correction of hypomagnesemia levels.

Discussion

As observed, patients on diuretics and chronic PPI are at a higher risk of hypomagnesemia. ⁴ By hindering gastrointestinal absorption of magnesium, PPI causes hypomagnesemia that may be refractory to oral magnesium, necessitating intravenous magnesium supplementation. ³

For our patient, differential diagnoses included hypomagnesemia, hypocalcemia, Wernicke's encephalopathy, CACNA1A channelopathy, encephalitis, and paraneoplastic syndromes. Proximal myopathy with raised CPK levels in association with ataxia have been described in hypomagnesemia. ⁵ Hypocalcaemia secondary to hypoparathyroidism is a close differential diagnosis, but hypocalcaemic myopathy is generally associated with pain. ⁶ The presence of myopathy, signs of neuronal hyperexcitability, DBN with a torsional component in the context of normal MRI brain is most consistent with the diagnosis of hypomagnesemia.

Movement disorders in association with hypomagnesemia include myoclonus, choreoathetosis, tetany, ⁷ tremors ⁸ and ataxia. ³ In the presence of ataxia, MR imaging shows T2/FLAIR hyperintensities in cerebellar hemispheres suggestive of cerebellar edema, that mimics cerebellitis and reversible cerebral vasoconstriction syndrome. ³ Brain imaging can be normal despite severe symptoms. ³

Eye movement abnormalities reported in association with hypomagnesemia include vertical nystagmus, ⁶ horizontal nystagmus, ⁷ transient torsional nystagmus. ⁹ DBN is a spontaneous nystagmus that occurs in primary gaze fixation and is characterized by fast downward and slow upward phases. ¹⁰

In a study of 117 patients, DBN was associated most commonly with neurodegenerative conditions such as spinocerebellar ataxia and treatable conditions such as posterior fossa lesion, paraneoplastic etiology associated with anti Yo antibodies, vitamin B12 ¹¹ and thiamine deficiency. ¹² In the absence of distinct anatomical lesion, DBN occurs as a result of dysfunctional GABAergic activity in the Purkinje cells of cerebellum, causing disinhibition of superior vestibular nucleus (SVN) leading to stimulation of oculomotor fibers supplying superior rectus muscle with subsequent slow upward gaze with corrective fast downgaze. ¹³

Although carpopedal spasm and Chvostek sign are classically described in the context of hypocalcaemia, these signs have also been observed in hypomagnesemia with normal or relatively mild hypocalcaemia. ⁵ Hence, in our patient, tremors, Chvostek sign and myoclonus were due to hypocalcaemia compounded by hypomagnesemia rather than hypocalcaemia being the sole cause. ⁶ Hypomagnesemia influences calcium mobilization from bones, parathyroid hormone (PTH) levels as well as bone resistance to PTH, leading to hypocalcemia. ¹⁴

Given the age of the patient and fluctuating course of the illness, autoimmune etiology such as GAD65 ¹⁵ was our first consideration. Moreover, the symptoms may improve with steroids, possibly as a result of resolution of cerebellar edema, ³ that can lead to misdiagnosis of an autoimmune disease. Hypomagnesemia must be considered if the symptoms are episodic, are associated with DBN, ataxia, tremors and myoclonus. Elevated CPK also points towards hypomagnesemia. Delayed diagnosis may lead to residual neurological deficits and cerebellar atrophy, ³ underscoring the need to establish the diagnosis early in the course of the illness.

Author Roles

(1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique.

S.R.: 1A, 1B,1C, 3A

V.V.K.: 1A, 3B

S.R.J.: 1B

R.K.N.: 1B

Disclosures

Ethical Compliance Statement: The authors confirm that the approval of an institutional review board was not required for this work. Informed consent was obtained from patient and his son. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding Sources and Conflicts of Interest: This study has not received any funding. The authors have no conflict of interest.

Financial Disclosures for the Previous 12 Months: None of the authors have any financial disclosure to make.