Neurol Sci DOI 10.1007/s10072-013-1620-5
LETTER TO THE EDITOR
A case of strio-pallido-dentate calcinosis associated with micromolecular myeloma N. Gueli • W. Verrusio • V. M. Magro M. Zaccone • M. Cacciafesta
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Received: 3 July 2013 / Accepted: 24 December 2013 Ó Springer-Verlag Italia 2014
Sirs, Fahr’s disease (FD) is a neurodegenerative disease whose aetiology is unknown, characterized by neuropsychiatric and motor problems associated with symmetrical, bilateral calcification of the basal ganglia. A drop in the metabolism and cerebral flow is deemed to be responsible for the onset of psychiatric and motor problems, cognitive deficit, painful symptoms and altered state of consciousness. The term Fahr’s syndrome (FS) is used when an etiological cause responsible for calcification can be identified. Fahr’s syndrome is associated with extremely diverse clinical conditions: calcium/phosphate metabolism disorders (hypo-hyperparathyroidism, pseudo-hypoparathyroidism), systemic lupus erythematosus, encephalitis and neoplasms [1]. Here, we describe clinical and radiological findings of a case of FS associated with micromolecular myeloma and hypothesize that bone remodelling could encourage the depositing of calcium at an intracerebral level as a result of an increase in the levels of alkaline phosphatase (ALP) and alteration of calcium levels. In January 2013, an 82-year-old woman was admitted to our hospital. The patient’s medical records showed a condition of severe osteoporosis with multiple collapsed vertebrae, dysphagia and rapidly ingravescent cognitive impairment over the last 18 months. No motor problems or psychiatric disturbances were reported. An acute onset of drowsiness made it necessary to hospitalize the patient, N. Gueli W. Verrusio (&) V. M. Magro M. Zaccone M. Cacciafesta Department of Anesthesiological, Cardiovascular, Respiratory, Nephrological, and Geriatric Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy e-mail:
[email protected]
who appeared to be in generally serious conditions (Glasgow coma score (GCS) 10/15), and prompted us to perform a brain CT. The brain CT scan was negative regarding focal densitometric alterations and localized accumulation of blood, but showed dystrophic calcification of the dentate nuclei with bilateral occipital cortical calcification at the level of the calcarine cortex, as seen in FD (Fig. 1). Blood chemistry analysis also showed: kidney failure (GFR 13 ml/min); anaemia (Hb 9.5 g/dl; n.v. 12–16 g/dl); hypercalcaemia (13.3 mg/dl; n.v. 8.40–10 mg/dl) and hyperphosphatemia (5.9 mg/dl; n.v. 2.8–4.6 mg/dl); increase of ALP (123 U/l; n.v. 35–104 U/l) and inflammatory markers (VES 69 mm/h; n.v. 0–35 mm/h; PCR 18,600 lg/l; n.v. \5,000 lg/l). Protein electrophoresis test showed hypoalbuminemia (33.8 g/l; n.v. 40.2–47.6 g/l), increase of acute phase proteins and hypogammaglobulinemia (8 % n.v. 11.1–18.8 %). Alterations of the calcium and phosphate metabolism are the most common cause of FS. In our patient, the concomitance of calcification of the basal ganglia and hypercalcaemia led us to suspect a condition of secondary FS and hyperparathyroidism, but subsequent serum assays for parathormone (PTH) (40.7 pg/ml; n.v.15–65 pg/ml) and vitamin D (31 ng/ml; n.v. [30 ng/ml) were normal in both cases. During the clinical course, the patient was less drowsy and suffered extremely painful symptoms, visual analogue scale (VAS) 10/10; worsening renal function was also noted. Even though drowsiness and painful symptoms could be attributed to cerebral calcification, was ingravescent kidney failure simply a concomitant pathological condition or was there a link among the clinical picture, calcification of basal ganglia and renal dysfunction? A 24-h urine collection showed significant proteinuria (2,777 mg/ 24 h; n.v. 40–150 mg/24). The finding of proteinuria in the
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Neurol Sci
Fig. 1 Images of hyperdensity, visible from brain CT scan without contrast medium, at the level of the cerebellar dentate nuclei and (less clearly) of the lenticular nuclei, bilaterally, to be attributed to intercerebral calcification
absence of significant albuminuria, the electrophoresis of hypogammaglobulinemia, the presence of extremely painful symptoms as well as the multiple collapsed vertebrae prompted us to perform immunofixation of both urine, which showed a significant level of Bence-Jones kappa proteins (1,760 mg/l with n.v. 69–93.4), and of serum, which showed a component with kappa immunoreactivity not associated with any immunoreactivity for immunoglobulin heavy chains. Hence, the diagnosis was micromolecular kappa myeloma. A subsequent full-body CT scan highlighted multiple, diffuse lytic bone lesions. The case of an elderly woman with bilateral basal ganglia calcification and no pathognomonic symptoms of FS—cognitive impairment was the only neurological sign that could be referred to FS—is here reported. A study showed that men with basal ganglia calcification had a higher incidence of symptoms and signs compared with women [2]. The exact pathogenetic process of strio-pallido-dentate calcinosis, probably multifactorial, is still unknown. Elevated calcium levels are thought to play a role in the pathogenesis of neurodegenerative brain disorders. Disorders of calcium metabolism should be excluded since they are the most common cause of intracranial calcification with a strio-pallido-dentate distribution. The intracellular overload of calcium levels produces oxidative stress that affects glial cells and neurons, causing a general metabolic failure. While hypercalcaemia associated with CT calcifications induces the diagnostic suspect of parathyroid disturbances, hypercalcaemia in the presence of normal levels of PTH opens the differential diagnosis among its possible causes. Comparison of the biochemical parameters in patients with and without basal ganglia calcification showed higher levels of ALP in subjects with
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calcifications [3]. As a matter of fact, the precipitation of calcium phosphate in specific cerebral areas, such as the basal ganglia, would be facilitated by the high concentration of ALP and iron in these areas. ALP is known to be a major enzyme in the process of calcification and phosphate ions are assumed to precipitate in calcium deposits under the influence of ALP activity: an increased activity of ALP in basal ganglia is then assumed [4]. Extensive bone remodelling, as seen in the course of myeloma, could encourage the depositing of calcium at an intracerebral level as a result of an increase in the levels of ALP and alteration of calcium levels. Moreover, other neoplasms described in association with this syndrome, such as acute lymphoblastic leukaemia and germinoma, are characterized by high levels of ALP, and so the levels of this enzyme may represent a predisposition to the genesis of FS [5]. Nevertheless, further studies are needed in relation to the various factors involved in the genesis of cerebral calcification. To our knowledge, there is no other mention in the literature of Fahr’s syndrome in association with micromolecular myeloma, both of which are rare conditions.
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Neurol Sci 4. Adachi M, Wellman KF, Volk BW (1968) Histochemical studies on the pathogenesis of idiopathic non-arteriosclerotic cerebral calcification. J Neuropathol Exp Neurol 27:483–499 5. Nishiyama K, Honda E, Mizuno T, Sakuta M, Kawakami H (1991) A case of idiopathic, symmetrical non-arteriosclerotic,
intracerebral calcification (Fahr’s disease) associated with M-proteinemia, followed by multiple myeloma. Rinsho Shinkeigaku 31(7):781–784
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