Neurology -- Correspondence for Koller et al., 62 (5) 730-733

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Correspondence published:

Effect of levodopa treatment for parkinsonism in welders: A double-blind study: Nai-Shin Chu, MD, PhD (19 May 2004)

Reply to Chu: William C. Koller, MD, Kelly E. Lyons (19 May 2004)

Untitled: Nai-Shin Chu, MD, PhD, Chin-Chang Huang, MD (17 May 2004)

Effect of levodopa treatment for parkinsonism in welders: A double-blind study 19 May 2004

Nai-Shin Chu, MD, PhD,
Chang Gung Medical College and Memorial Hospital
Department of Neurology, Chang Gung Memorial Hospital, 199 Tung Hwa North Road, Taipei 10591, Taiwan
Send Correspondence to journal:
Re: Effect of levodopa treatment for parkinsonism in welders: A double-blind study

chu060{at}cgmh.org.tw Nai-Shin Chu, MD, PhD

We read with interest the article by Koller et al.[1] dealing with levodopa therapy in 13 career welders with a presumptive diagnosis of manganese (Mn)-induced parkinsonism.

Because the diagnosis of Mn-induced parkinsonism was based solely on the presence of parkinsonian signs and a history of long-term exposure to manganese in welding rods,we are concerned about the validity of such a diagnosis for the following reasons:
1. There was a lack of Mn exposure data, including air monitoring in the working place and evidence of exposure in the welders by measuring Mn in the blood, urine, or hair. Neuro-imaging studies, including MRI, fluoro-dopa uptake PET, or dopamine-transporter SPECT, were not performed. Those studies might help differentiate Mn parkinsonism from idiopathic Parkinson's diseases (PD), other types of parkinsonism and degenerative diseases. Therefore, whether those patients had an exposure to high concentrations of Mn remained uncertain.
2. It is often difficult to differentiate between PD and Mn parkinsonism based mainly on clinical manifestations[2]. The parkinsonian signs of those patients were not necessarily indicative of Mn-induced parkinsonism, particularly in the presence of rest tremor in some patients and the absence of dystonia in all patients. Although gait abnormality is common in Mn parkinsonism, types of gait disturbance were not provided. The older age of disease onset in those patients suggests that at least some of the patients might have PD or other types of parkinsonism. The diagnostic uncertainly was further increased by the fact that the specialty and experiences of the physician who made the diagnosis were not mentioned.
The relationship between welding exposure and development of parkinsonism has not been firmly established. The claim is based mainly on a few cases or incomplete neurological work-up in field survey[3,4]. Interestingly, in a recent study involving 15 career welders, their parkinsonism was clinically not different from PD except for a younger age at onset[5]. The findings of the fluoro-dopa PET study from two patients were also typical of PD. It was concluded that welding might be an environmental risk factor for PD. These studies seem to suggest that in the parkinsonism of career welders, it is crucial to rule out the possibility of PD or other types of parkinsonism, particularly in those patients with an older age at onset.
Whether long-term welding exposure may cause Mn-induced parkinsonism is still unclear. However, it is essential to carry out environmental and personal exposure studies if Mn-induced parkinsonism is suspected.
References
1. Koller WC, Lyons KE, Truly W. Effect of levodopa treatment for parkinsonism in welders. A double-blind study. Neurology 2004; 62: 730- 733.
2. Calne DB, Chu NS, Huang CC, Lu CS, Olanow W. Manganism and idiopathic parkinsonism: similarities and differences. Neurology 1994; 44: 1583-1586.
3. Tanaka S, Lieben J. Manganese poisoning and exposure in Pennsylvania. Arch Environ Health 1969; 19: 674-684.
4. Chandra SV, Shukla GS, Srivastava RS, Singh H, Gupta VP. An exploratory study of manganese exposure to welders. Clin Toxicol 1981; 18: 407-416.
5. Racette BA, McGee-Minnich L, Moerlein SM, Mink JW, Videen TO, Perlmutter JS. Welding-related parkinsonism: clinical features, treatment, and pathophysiology. Neurology 2001; 56: 8-13.

Reply to Chu 19 May 2004

William C. Koller, MD,
Mount Sinai School of Medicine
1 Gustave L. Levy Place, NY, NY 10029,
Kelly E. Lyons
Send Correspondence to journal:
Re: Reply to Chu

william.koller{at}mssm.edu William C. Koller, MD, et al.

Dr. Chu raises several important issues regarding the diagnosis of toxin-induced parkinsonism. To address his specific questions:
1. As stated in table 1, the mean years of exposure in these patients was 25.2 years. More specific exposure data was not included as this was a pharmacological study. Most of the patients were no longer working therefore measuring manganese in the blood or urine or obtaining an MRI scan would be of no value. We agree that neuroimaging of the dopamine system would most likely be helpful in the differential diagnosis. However, there is minimal data for neuroimaging in manganese intoxication and what exactly there studies would tell us is uncertain. However if a fluorodopa PET scan is normal the diagnosis of Parkinson�s disease would be unlikely.
2. We also believe that this is a broad spectrum of clinical phenotypes for the various forms of parkinsonism. Regarding our paper, we are confident that one of the authors (WCK) can recognize parkinsonism. The diagnosis of manganese induced parkinsonism was a presumptive one, as stated, for the purpose of the study. We used the term parkinsonism in welders as a descriptive term. We also acknowledged the diagnostic uncertainty in these patients
3. We agree that the diagnosis of different types of parkinsonism may be difficult. There are few biomarkers that are useful in this regard. This is why we did this study to see if levodopa responsiveness can be useful in separating various forms of parkinsonism, which it appears to be, as Dr. Chu has reported previously. [1]
4. Lastly, a case of parkinsonism due to manganese in a welder has been reported which addresses many of the diagnostic concerns of Dr. Chu. [2]
We agree that more scientific investigation is necessary regarding toxins that cause parkinsonism.
References
1.Lu, CS, Huang, CC, Chu, NS, Calne, DB. Levodopa failure in chronic manganism. Neurology 1994; 44:1600-1622
2.Sadek, AH, Rauch, R, Schulz, PE. Parkinsonism due to manganism in a welder. Int. J. Tox 2003; 22:393-401

Untitled 17 May 2004

Nai-Shin Chu, MD, PhD,
Chang Gung Medical College and Memorial Hospital
Department of Neurology, Chang Gung Memorial Hospital, 199 Tung Hwa North Road, Taipei 10591, Taiwan,
Chin-Chang Huang, MD
Send Correspondence to journal:
Re: this article

chu060{at}cgmh.org.tw Nai-Shin Chu, MD, PhD, et al.

We read with interest the article by Koller et al.[1] dealing with levodopa therapy in 13 career welders with a presumptive diagnosis of manganese (Mn)-induced parkinsonism.
Because the diagnosis of Mn-induced parkinsonism was ��based solely on the presence of parkinsonian signs and a history of long-term exposure to manganese in welding rods,�� we are concerned about the validity of such a diagnosis for the following reasons:
1. There was a lack of Mn exposure data, including air monitoring in the working place and evidence of exposure in the welders by measuring Mn in the blood, urine, and/or hair. Neuro-imaging studies, including MRI, fluoro-dopa uptake PET, and/or dopamine-transporter SPECT, were not performed. Those studies might help differentiate Mn parkinsonism from idiopathic Parkinson��s diseases (PD), other types of parkinsonism and degenerative diseases. Therefore, whether those patients had an exposure to high concentrations of Mn remained uncertain.
2. It is often difficult to differentiate between PD and Mn parkinsonism based mainly on clinical manifestations[2]. The parkinsonian signs of those patients were not necessarily indicative of Mn-induced parkinsonism, particularly in the presence of rest tremor in some patients and the absence of dystonia in all patients. Although gait abnormality is common in Mn parkinsonism, types of gait disturbance were not provided. The older age of disease onset in those patients suggests that at least some of the patients might have PD or other types of parkinsonism. The diagnostic uncertainly was further increased by the fact that the specialty and experiences of the physician who made the diagnosis were not mentioned.
The relationship between welding exposure and development of parkinsonism has not been firmly established. The claim is based mainly on a few cases or incomplete neurological work-up in field survey[3,4]. Interestingly, in a recent study involving 15 career welders, their parkinsonism was clinically not different from PD except for a younger age at onset[5]. The findings of the fluoro-dopa PET study from 2 patients were also typical of PD. It was concluded that welding might be an environmental risk factor for PD. These studies seem to suggest that in the parkinsonism of career welders, it is crucial to rule out the possibility of PD or other types of parkinsonism, particularly in those patients with an older age at onset.
At present, whether long-term welding exposure may cause Mn-induced parkinsonism still remains unsettled. However, it is essential to carry out environmental and personal exposure studies if Mn-induced parkinsonism is suspected.
References
1. Koller WC, Lyons KE, Truly W. Effect of levodopa treatment for parkinsonism in welders. A double-blind study. Neurology 2004; 62: 730- 733.
2. Calne DB, Chu NS, Huang CC, Lu CS, Olanow W. Manganism and idiopathic parkinsonism: similarities and differences. Neurology 1994; 44: 1583-1586.
3. Tanaka S, Lieben J. Manganese poisoning and exposure in Pennsylvania. Arch Environ Health 1969; 19: 674-684.
4. Chandra SV, Shukla GS, Srivastava RS, Singh H, Gupta VP. An exploratory study of manganese exposure to welders. Clin Toxicol 1981; 18: 407-416.
5. Racette BA, McGee-Minnich L, Moerlein SM, Mink JW, Videen TO, Perlmutter JS. Welding-related parkinsonism: clinical features, treatment, and pathophysiology. Neurology 2001; 56: 8-13.