LETTER TO THE EDITORS

Falling too Fahr

Arianna Merlini • Luca Peruzzotti-Jametti • Marco Bacigaluppi •

Giovanna Mantovani • Annamaria Spada • Mariaemma Rodegher •

Giancarlo Comi

Received: 30 November 2011 / Revised: 4 January 2012 / Accepted: 5 January 2012 / Published online: 21 January 2012

� Springer-Verlag 2012

Dear Sirs,

Repeated falls are a frequent complaint of patients referring

to neurology units [1]. The most prevalent causes are sei-

zures, neurogenic and cardiac syncopes, vestibulopathies,

and neurological disorders affecting gait and balance [2].

Nevertheless, other less common etiologies—e.g., cata-

plexy, drop attacks, hyperekplexia and tetany—may mimic

neurologic or cardiovascular disturbances [3]. In this case

report, we propose a rare yet relevant cause of recurring falls

that should be kept in mind during differential diagnosis.

A 19-year-old Asian woman presented to our emergency

room for repeated falls characterized by stiffening of the four

limbs. History-taking revealed that she had suffered since

infancy from carpopedal spasms and sparse episodes of

generalized muscle rigidity, which, however, had never been

investigated. In the last weeks, an increase in the frequency of

falls and spasms brought her to finally seek medical attention.

During clinical examination, the patient suddenly fell

backwards with a generalized tonic contraction that rever-

ted within a minute, while a moderate hypertonus persisted

over time. The diffuse cramps, repeated attacks of tonic

spasms, and sustained hypertonus were all suggestive for

generalized tetany. Consistently, Chvostek’s and Trous-

seau’s signs were found positive (Online Resource 1).

Tetany is a condition of enhanced neuromuscular excit-

ability, most frequently associated with electrolyte alterations

[4]. Indeed, blood tests showed a remarkable hypocalcemia

(1.13 mmol/l [reference interval 2.1–2.6]) with a prolonged

corrected QT interval (0.470 s [r.i. B 0.450]) on electrocar-

diogram (ECG).

To avoid further tetanic crises and cardiac complications,

intravenous calcium gluconate was immediately started.

Afterwards, brain-CT scan was performed, revealing

widespread calcifications of grey–white matter junction, basal

ganglia, thalamus, and dentate nuclei (Fig. 1). This pattern of

striopallidal-dentate calcifications is commonly referred to as

‘Fahr’s disease’, a misnomer, and can be encountered in

numerous chronic conditions, including persistent distur-

bances of phosphate/calcium metabolism [5]. This finding

suggested that the tetanic crises of our patient were more likely

the expression of an underlying chronic metabolic syndrome,

rather than an isolated episode of hypocalcemia. Thus, we

conducted an extended metabolic panel that revealed reduced

serum 25-OH vitamin D (7.6 ng/ml [r.i. 10–68]) and ionized

calcium (0.64 mmol/l [r.i. 1.18–1.3]) with increased phos-

phate (2.51 mmol/l [r.i. 0.8–1.5]) and parathyroid hormone

(PTH, 349 pg/ml [r.i. 17.3–72.9]).

Hypocalcemia, hyperphosphatemia, and high PTH are

the hallmarks of pseudohypoparathyroidism (PHP), a rare

A. Merlini, L. Peruzzotti-Jametti, and M. Bacigaluppi contributed

equally to this work.

Electronic supplementary material The online version of thisarticle (doi:10.1007/s00415-012-6411-z) contains supplementarymaterial, which is available to authorized users.

A. Merlini (&) � L. Peruzzotti-Jametti � M. Bacigaluppi �M. Rodegher � G. Comi

Department of Neurology and Neurophysiology, Institute of

Experimental Neurology, San Raffaele Scientific Institute,

Via Olgettina 58, 20132 Milan, Italy

e-mail: merlini.arianna@hsr.it

A. Merlini � L. Peruzzotti-Jametti � M. Bacigaluppi

Neuroimmunology Unit, Institute of Experimental Neurology,

San Raffaele Scientific Institute, Via Olgettina 58,

20132 Milan, Italy

G. Mantovani � A. Spada

Endocrinology and Diabetology Unit, Department of Medical

Sciences, Universita degli Studi di Milano, Fondazione IRCCS

Ca’ Granda Ospedale Maggiore Policlinico,

Via Francesco Sforza, 35, 20122 Milan, Italy

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J Neurol (2012) 259:1483–1484

DOI 10.1007/s00415-012-6411-z

disease characterized by end-organ resistance to PTH [6].

Different subtypes of PHP have been described as conse-

quence of mutations in the guanine nucleotide binding

protein alpha stimulating (GNAS) complex locus [7]. In

our patient, genetic testing revealed an imprinting defect

with loss of methylation of the exon A/B and a deletion of

3-kb in the STX16 gene within the GNAS locus, indicative

of pseudohypoparathyroidism type 1b [8].

Treatment with calcium supplementation and 1,25-di-

hydroxyvitamin D3 is recommended in these cases and

leads to full resolution of tetany, falls, and ECG abnor-

malities. In our patient, the delayed diagnosis led to the

permanent sequelae of striopallidal-dentate calcifications,

‘‘Fahr’s disease’’, that, despite being asymptomatic in 32%

of cases [9], may severely condition the prognosis causing

parkinsonism, dyskinesias, seizures, and dementia [10–12].

Despite being a common manifestation, all too often the

diagnosis of recurring falls remains elusive [13], with a

considerable burden on morbidity and mortality, as well as

costs for unavailing investigations. On that note, general-

ized tetany is seldom encountered in clinical practice and

rarely considered for differential diagnosis [3, 14]. Our

case highlights how, even nowadays, bearing in mind the

clinical and biochemical features of tetany and its excep-

tional causes may ease a complex diagnosis, direct early

treatment, and change the patient’s prognosis.

Conflicts of interest The authors declare that they have no conflicts

of interest.

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Fig. 1 Axial CT images

showing in a bilateral

calcifications in the dentate

nuclei (black-filled arrowheads)

and in b symmetric

calcifications of basal ganglia

and thalamus (putamen, nuclei

caudati, globi pallidi, black-rimmed arrowheads) and of the

grey–white matter junction

(black-filled arrowheads)

1484 J Neurol (2012) 259:1483–1484

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